Funds received from Core Voluntary Contributions and Assessed Contributions for 2014-2015 covered the costs associated with this guideline update.

# Executive summary

# Background and objectives
Mental, neurological, and substance use (MNS) disorders are prevalent in all regions of the world and are major contributors to morbidity and premature mortality. In 2008, the World Health Organization (WHO) developed the Mental Health Gap Action Programme (mhGAP), to facilitate scaling up of care for MNS disorders. A key part of mhGAP is the evidence-based guideline, published in 2010 and available through the mhGAP Evidence Resource Centre (/). The objectives of the guideline are:
- To provide up-to-date WHO guidance to facilitate delivery of interventions by non-specialist health care providers in low-and middle-income countries (LAMICs);
- To assist with the scale up of care for MNS disorders identified as conditions of high priority in LAMICs, specifically: depression, psychosis (including schizophrenia and bipolar disorders), epilepsy, child mental disorders, dementia, alcohol use disorders, drug use disorders and self-harm/suicide;
- To provide up-to-date WHO guidance that will facilitate the implementation of the WHO Comprehensive Mental Health Action Plan 2013-2020 by health care planners and programme managers in LAMICs.
As evidence-based guidelines are designed to reflect current research, regular update is of paramount relevance. 1 Out-of-date recommendations could be one determinant of inadequate patient care: therefore, conducting regular evaluations and performing updates when appropriate should ensure the validity of recommendations. More than four years have passed since the mhGAP recommendations have been issued. Since then, regular monitoring of the background evidence has been performed by the WHO Collaborating Centre assisting with the mhGAP guideline process in order to highlight areas where update is appropriate. Furthermore, feedback from technical experts and health care providers has been collected, together with feedback from several implementation activities. All of these activities prompted WHO to consider that, in order to maintain the validity of the mhGAP guideline, an update is warranted.

# Target audience
The primary audience for the mhGAP guideline are non-specialized health-care providers working at firstand second-level health-care facilities. These include physicians who are not mental health specialists, family physicians, nurses and clinical officers or other cadres of health workers. The secondary audience includes health care managers including national, regional and district level programme managers responsible for primary or non-mental health secondary health care services and specialists (in mental health, neurology and substance use) involved in training of trainers and supervision.

# Guideline update methodology
The Guideline Development Group (GDG) members, the technical experts (to assist with evidence review and synthesis), and the peer reviewers were selected from an international panel of experts with multidisciplinary expertise. The evidence review and synthesis process as well as the recommendations were developed in accordance with the procedures outlined in the WHO Handbook for Guideline Development.

# Methods for evidence synthesis
The key questions from the current mhGAP guideline were reviewed and areas where update was appropriate were identified based on the feedback from implementation activities, health care providers and regular monitoring of evidence. New key questions were identified based on the feedback received from users of the mhGAP guideline in the countries. There were 29 key questions used to update the guideline. These were formulated using the PICO framework (Population, Intervention, Comparator, Outcome). The review and synthesis of evidence was carried out through systematic searches. For each of the key questions included in the update process, an evidence profile was constructed using WHO guideline development procedures. Evidence profiles summarise the evidence retrieved, provide the assessment of the quality of evidence wherever possible using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and present discussion of values, preferences, benefits, harms and feasibility.

# Translating evidence into recommendations
Within the evidence profile, the section entitled "evidence to recommendations" presents a synopsis of the evidence (benefits and harms of the intervention) and the quality of evidence according to the GRADE approach, and it discusses values and preferences and the feasibility of the intervention under consideration. Based on the evaluation of the above criteria, the GDG proposed the strength of each recommendation as either strong or conditional.
A "strong" recommendation suggests that the GDG agreed that the quality of the evidence combined with certainty about the values and preferences and the feasibility of the recommendation meant it should be followed in all or almost all circumstances. A "conditional" recommendation suggests less certainty about the quality of evidence and variation values and preferences and feasibility, leading to circumstances in which the recommendation may not apply.

# Summary of recommendations
The following table summarizes the recommendations for the mhGAP Guideline Update 2015. They should be read together with their corresponding remarks reported later in this document. Definition and description of interventions, together with the evidence retrieved and analysis of values and preferences and feasibility issues leading to these recommendations can be found in individual evidence profiles. As first-line therapy, health care providers may select psychological treatments (such as behavioural activation cognitive behavioural therapy or interpersonal psychotherapy or antidepressant medication (such as selective serotonin reuptake inhibitors  and tricyclic antidepressants. They should keep in mind the possible adverse effects associated with antidepressant medications, the ability to deliver either intervention (in terms of expertise, and/or treatment availability), and individual preferences. Health care providers can offer different treatment formats of WHO's recommended, structured psychological interventions for adults and older adolescents with depressive disorder. These include behavioural activation, cognitive behavioural therapy (CBT), interpersonal psychotherapy (IPT), problem-solving treatment as an adjunct treatment (e.g. in combination with antidepressants). Different treatment formats for consideration include (a) individual and/or group face-to-face psychological treatments delivered by professionals and supervised lay therapists, as well as (b) self-help psychological treatment.
While face-to-face psychological treatment or guided self-help psychological treatment are likely to have better outcomes than unguided self-help, the latter may be suitable for those people who either (a) do not have access to face-to-face psychological treatment or guided self-help psychological treatment or (b) are not willing to access such treatments.
(Conditional recommendation. Low quality of evidence.)
Psychosis including schizophrenia and bipolar disorder

# PSY1. Role of depot antipsychotic medication in long-term antipsychotic treatment
In people with psychotic disorders (including schizophrenia) requiring long-term antipsychotic treatment, depot antipsychotics can be offered instead of oral medications as part of a treatment plan.
(Conditional recommendation. Very Low quality of evidence.)

# PSY2. Antipsychotics and mood stabilizers (lithium, valproate, or carbamazepine) for maintenance treatment of bipolar disorder
Lithium or valproate or certain second-generation antipsychotics (aripiprazole, olanzapine, paliperidone extended release, quetiapine, and risperidone long acting injection release) can be offered for the maintenance treatment of bipolar disorder. If treatment with one of these agents is not feasible, first-generation antipsychotics or carbamazepine may be used. Maintenance treatment should be offered in primary health care settings under supervision of a specialist. Recovery-oriented psychosocial interventions (e.g. life skills and social skills training) to enhance independent living skills can be offered for people with psychotic disorders (including schizophrenia and bipolar disorder) and for their families and/or caregivers.
Facilitation of assisted living, independent living and supported housing that is culturally and contextually appropriate may be considered as an option for people with psychotic disorders (including schizophrenia and bipolar disorder). Careful consideration should be given to the functional capacity and the need for stability and support when advising and facilitating optimal housing arrangements.
(Conditional recommendation. Very Low quality of evidence)

# PSY4. Recovery-oriented strategies enhancing vocational and economic inclusion (such as supported employment)
Recovery-oriented strategies enhancing vocational and economic inclusion (e.g. supported employment) can be offered for people with psychosis (including schizophrenia and bipolar disorder). Such strategies should be contextualised to their social and cultural environment, using formal and non-formal recovery-oriented interventions that may be available, and using a multisectoral approach.
(Conditional recommendation. Low quality of evidence)

# PSY5. Second-generation antipsychotic medications in psychotic disorders (including schizophrenia)
Second-generation antipsychotics (with the exception of clozapine which is indicated for treatment resistant psychosis) can be offered for the treatment of psychotic disorders (including schizophrenia). There is no clinically relevant advantage of one second-generation antipsychotic over others and choice should be based on availability, cost, patient preferences and possible adverse effects associated with each medication.
(Conditional recommendation. Low quality of evidence)

# PSY6. Pharmacological interventions in adolescents with psychotic disorders (including schizophrenia and bipolar disorder)
In adolescents with psychotic disorders (including schizophrenia and bipolar disorder), certain second-generation antipsychotic medications (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone) can be offered as a treatment option under supervision of a specialist.
If treatment with one of the above agents is not feasible, first-generation antipsychotics (haloperidol, chlorpromazine, perphenazine, molindone) may be used under supervision of a specialist. As evidence-based guidelines are designed to reflect current research, regular update is of paramount relevance. 6 Out-of-date recommendations could be one determinant of inadequate patient care: therefore, conducting regular evaluations and performing updates when appropriate should ensure the validity of recommendations.
More than four years have passed since the mhGAP recommendations have been issued. Since then, regular monitoring of the background evidence has been performed by the WHO Collaborating Centre assisting with the mhGAP guideline process in order to highlight areas where update is appropriate. Furthermore, feedback from technical experts and health care providers has been collected, together with feedback from several implementation activities. All of these activities prompted WHO to consider that, in order to maintain the validity of the mhGAP guideline, an update is warranted.

# WHO guidelines and products related to the existing and updated guidelines
The updated mhGAP guideline will be used to maintain the validity of the mhGAP Evidence Resource Centre: a repository of background material, process documents, evidence profiles and recommendations in electronic format, organized around the mhGAP priority conditions (/).
The mhGAP guideline also forms the basis of mhGAP derivative materials, including the mhGAP Intervention Guide (mhGAP-IG) and implementation materials. The mhGAP-IG is a technical tool, based on the mhGAP guideline, which gives guidance for the management of MNS disorders, developed for non-specialist health settings (/). Other mhGAP implementation materials developed to assist countries in implementing the mhGAP guideline and interventions include mhGAP training materials, as well as other toolkits and process documents.
There are other relevant guidelines: A Guideline for the management of conditions specifically related to stress (/) and a guideline for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence (/). These guidelines were produced in 2013 and 2014 respectively; therefore, they are not due to be updated and were not included in this guideline update.
Some recommendations from the mhGAP updated guideline on epilepsy and seizures will be linked to Paediatric Emergency Triage Assessment and Treatment Guidelines on Fluids, Oxygen therapy and Seizures, which are currently being finalized.

# Objectives of the Guideline update
This guideline is an update of the existing mhGAP guideline for MNS disorders.
The mhGAP guideline has the following objectives:
- To provide up-to-date WHO guidance to facilitate delivery of interventions by non-specialist health care providers at primary and secondary care facilities in LAMICs.
- To assist with the scale up of care for MNS disorders identified as conditions of high priority in LAMICs, specifically: depression, psychosis (including schizophrenia and bipolar disorders), epilepsy, child mental disorders, dementia, alcohol use disorder, drug use disorders and self-harm/suicide.  To provide up-to-date WHO guidance that will facilitate implementing the WHO Comprehensive Mental Health Action Plan 2013-2020 by health care planners and programme managers in LAMICs.

# Target audience
This guideline update focuses on the same target audience as for the first edition of mhGAP guideline: health care providers working at a first-or second-level facility or at district level, including basic outpatient and inpatient services. The health care providers could be doctors, nurses or other cadres of health workers. It is also aimed to be used by health care planners and programme managers including national, regional and district level programme managers responsible for primary or non-mental health secondary care services and specialists (in mental health, neurology and substance use) involved in training of trainers and supervision.

# Scope of guideline: What is included in this update?
The first edition of the mhGAP guideline included guidance on evidence-based interventions to identify and manage a number of priority conditions (depression, psychosis, bipolar disorders, epilepsy and seizures, mental disorders in children and adolescents, dementia, alcohol use disorders, drug use disorders, and selfharm/suicide). These priority conditions were selected because they represent a large burden in terms of mortality, morbidity and disability, have high economic costs, and are associated with human rights violations.
The list of key questions and recommendations issued in 2010 were reviewed for the update process. After the publication of the 2010 mhGAP guideline, more evidence and programmatic experience has become available. This revision took the following factors into careful consideration:
(a) New evidence that has been produced: From 2010 onwards regular updates of the evidence base have been carried out using appropriate search strategies;
(b) Feedback from WHO implementation activities: From 2010 onwards, WHO has implemented several programmes in LAMICs that were based on mhGAP recommendations and has also collected suggestions and proposals for future revisions;
(c) Feedback from experts and health care providers: Feedback was collected from international experts and health care providers who are familiar with using mhGAP recommendations and related products by means of a standardized form.
Based on the review process, the key questions issued in 2010 were stratified into one of the following four categories (see Figure 1): -same population, intervention, comparison and outcome (PICO), no significant new evidence: no change;
-same PICO but significant new evidence: update existing evidence profile and recommendation; -changed PICO: update existing evidence profile and recommendation; -new key question, new PICO: draft new evidence profile and recommendation.
In consultation with the Guideline Development Group (GDG), the key questions were then finalized for evidence review and synthesis process. No modification of the overall scope of the guidelines was done after initial approval of the update plan by the WHO Guideline Review Committee. Based on the feedback of GDG members and according to evidence availability and programmatic experience, the key questions were further refined.
Figure 1. Flow chart describing the process followed to identify key questions and recommendations to be updated, and new key questions to be developed

# Guideline update methodology
The mhGAP 2015 guideline update compiles 29 evidence-based recommendations for the following priority MNS disorders: depression, psychosis and bipolar disorders, epilepsy and seizures, child and adolescent mental disorders, dementia, alcohol use disorders, drug use disorders and self-harm and suicide.
The guideline development process followed the methods outlined in the WHO Handbook for Guideline Development 7. The evidence quality assessment was conducted following GRADE methodology, where applicable. For each of the included key questions, an evidence profile was constructed summarizing the evidence retrieved, the GRADE quality assessment and discussion of values, preferences, benefits, harms and feasibility. The recommendations were then finalized by the GDG considering all of the above criteria.

# Group process WHO Guideline Secretariat
In order to oversee the guideline update process and evidence synthesis, WHO's Department of Mental Health and Substance Abuse coordinated the process of guideline development. In addition, other relevant WHO departments were consulted to advise and give feedback on the guideline development process (see Acknowledgment section).

# Guideline Development Group
The Guideline Development Group (GDG) was convened to advise on the content and process, interpretation of evidence and to formulate and finalize the recommendations. The GDG included experts with multidisciplinary expertise relevant to the guideline and with adequate regional and gender representation (see Appendix 1). Regular discussions with the GDG took place by email and conference calls.
A GDG meeting was organized in December 2014 for the review of evidence and finalisation of recommendations.

# Peer Reviewers
A group of experts from different disciplines and regions, identified by the WHO secretariat and the GDG, reviewed the key questions during the initial stages of the guideline update process and also reviewed the final evidence profiles commenting on the evidence review process, clarity and implications for implementations (see Acknowledgment section).

# Declaration of Interest
Declarations of interest (DoI) were requested from GDG members, experts involved in the evidence review process and from peer reviewers. According to the WHO Handbook for Guideline Development, interests were reviewed as per the following categories: financial (any income or support that is related to, or could be affected by, the outcome of this guideline update) and academic and public positions (any interest that could be reasonably perceived to affect an individual's objectivity and independence while working on this guideline update). The following possibilities were foreseen: (a) the conflict of interest requires no action beyond declaration at the meeting and reporting in the final guideline; (b) the conflict of interest is significant but related to only some areas of the GDG work in which case the participant will not participate when the group considers these areas and will not have access to the relevant documents; (c) the conflict of interest is such that participation in the discussion is appropriate, but the member will be recused for development and ratification of recommendations; or (d) the conflict of interest is such as to preclude participation.

# Managing Conflict of Interest
The WHO secretariat noted any potential financial, academic and positional conflicts of interest and summarized these. In the case of a conflict of interest among GDG members, the WHO secretariat decided whether and to what extent the person could participate in the guideline development. GDG members declared potential conflicts of interest in their forms. A 'Note for the Record' was developed following consultation with the Director of the Department (see Appendix 2). The overview of declarations can be found in Appendix 3). At the GDG meeting in December 2014, the information on declaration of interest was presented as per the Note for the Record, and GDG members were given the opportunity to comment or express concern about declared interests of another group member. No further comments were received.

# Evidence synthesis
The evidence profiles and GRADE tables were developed according to the following process:
- The PICO questions were defined as previously described. The outcomes were selected and prioritized by WHO Secretariat in consultation with the GDG members.  The search strategy for each evidence profile was developed, in consultation with WHO librarian or other experts in information retrieval. Comprehensive searches of major bibliographic databases (see Appendix 4) were conducted in order to identify one or more systematic review(s) that match the PICO terms. When possible, high-quality and recent systematic reviews were used to draft evidence profiles. If only low-quality or not recent systematic reviews were identified, new systematic reviews were commissioned.  The evidence retrieval and synthesis was carried out as per the WHO Handbook for Guideline Development (see Figure 2).  The evidence profiles were developed according to the following structure:
-  The quality assessment was conducted according to the GRADE methodology 8. This considered study design (Randomized Controlled Trial  or observational studies), risk of bias, inconsistency, indirectness, imprecision and risk of reporting bias. The quality of evidence for each intervention was graded as high, moderate, low or very low according to the considerations listed. Quality of evidence is defined as the extent to which one could be confident that an estimate of effect or association was correct. The implications of these categories are detailed in Table 1. Guiding principles describing how to assess each of the criteria of the GRADE methodology were prepared in advance and provided to technical experts (see Appendix 5), to 8 The GRADE methodology can be found at 

# Table 1. The quality of evidence in GRADE

# Level of evidence
We are very confident that the true effect lies close to that of the estimate of the effect.
We are moderately confident in the effect estimate:. the true effect is likely to be close to the estimate of the effect but there is a possibility that it is substantially different.
Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.

# Very low
We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of the effect.

# WHO Handbook for Guideline Development, 2 nd edition 2014

# Translating evidence into recommendations
The 'Evidence to recommendation table' was included in the evidence profiles capturing benefits and/or harms, quality of evidence, values and preferences, feasibility, and the recommendation and remarks. The GDG considered benefits, harms, values, preferences and feasibility for developing the recommendation and its strength.

# Evidence on Benefits and Harms
The evidence on benefits and harms was summarized based on the review and synthesis process including the GRADE tables, along with the presentation of the quality of evidence.

# Values and Preferences
This section details issues that may give rise to preferences in favour of or against the intervention among those affected by the recommendation. Some of the values and preferences that were considered during the preparation of the evidence profiles and during the discussion with the GDG panel included:
This section considered the issues around feasibility and resource use based on GDG members and experts knowledge and experience from implementation of the guideline, especially in LAMICs. Some of the feasibility issues that were considered during the development of the evidence profiles, during GDG discussion and while drafting and finalising the recommendations and accompanying remarks included:

# Strength of recommendation
The strength of a recommendation expresses the degree to which the GDG is confident in the balance between the desirable and undesirable consequences of implementing the recommendation. When the GDG was very certain about this balance (i.e. the desirable consequences clearly outweigh the undesirable consequences), it issued a strong recommendation in favour of an intervention. When it was uncertain about this balance, however, it issued a conditional recommendation. The table below based on the WHO Handbook for Guideline Development provides an aid to interpreting the strength of a recommendation.

# Strong recommendation Conditional recommendation
Patients Most individuals in this situation would want the recommended course of action; only a small proportion would not.
Most individuals in this situation would want the suggested course of action, but many would not.
Most individuals should receive the intervention.
Different choices will be appropriate for individual patients, who will require assistance in arriving at a management decision consistent with his or her values and preferences.
The recommendation can be adopted as policy in most situations.
Policy-making will require substantial debate and involvement of various stakeholders.
In some cases the GDG proposed a strong recommendation even with low quality of evidence if the benefits of the intervention significantly outweighed the harms associated with the intervention or if there were strong values and preferences or because of feasibility of implementation. For example, if the quality of the evidence for an intervention is low, but not using the intervention could lead to the death of the patient, a strong recommendation was made. The rationale for the recommendations is included in the evidence profile with regards to the clinical evidence, values and preferences and feasibility.

# GDG meeting
The GDG meeting was held in Geneva, Switzerland in December 2014 with the aim to reach consensus on the mhGAP Guideline update recommendations. The evidence profiles were reviewed and discussed in detail. During the meeting, the GDG members considered the following:
Summary and the quality of the available evidence on benefits and harms ii.
Values, preferences and feasibility issues related to the recommended interventions in different settings iii.
The resource use implications of options available, mainly considering the perspectives of programme managers in low-resource settings

# Decision-making process
The decision-making process proposed was the following: After discussion, GDG members would reach an agreement on each recommendation based on the draft prepared by the WHO Secretariat. In the event of disagreements, the chair(s) and methodologist(s) would ascertain whether the disagreement is primarily related to the interpretation of data or the formulation of the recommendation. Draft recommendations would be revised accordingly in order to achieve unanimous agreement. If unanimous agreement was not reached, GDG members would vote on revised draft recommendations. Voting would be executed by raising hands. GDG members would have the option of having their objection recorded. In case of voting, consensus would be considered as the majority agreement of the guideline group members. WHO staff members present at the meeting, as well as other external technical experts involved in the collection and review of the evidence would not be allowed to vote.
Unanimous agreement by discussion was reached by GDG on all the recommendations and their rating and therefore, no voting was required.

# External peer review
The evidence profiles were circulated to external peer reviewers to comment on the clarity of the language and possible implications of the recommendations. The comments on each evidence profile were considered by the WHO Secretariat and GDG and incorporated as per the scope of each of the key questions included in the guideline update process.

# Publication, dissemination and evaluation of the guideline

# Presentation of the updated mhGAP guideline
The updated mhGAP guideline will be made available in the "mhGAP Evidence Resource Centre", a dedicated internet space on the WHO website where guideline materials can be found organized according to mhGAP priority condition: /. From the Evidence
Resource Centre, all the evidence profiles can be accessed with detailed information on available evidence, GRADE quality analysis, narrative descriptions of the evidence that was not inserted into GRADE tables and considerations on values and preferences and feasibility issues.

# Subsidiary products
The mhGAP guideline is developed in English: however, mhGAP products (which are derived from the guideline, including the mhGAP-intervention guide and training materials) will be developed and translated into other WHO official languages (depending upon availability of funding) for wider dissemination, and in collaboration with WHO Regional Offices.
The updated mhGAP guideline will be incorporated into an updated version of the mhGAP Intervention Guide (mhGAP-IG) for mental, neurological and substance use disorders in non-specialized health settings (version 2.0). The mhGAP-IG translates the evidence-based recommendations into simple clinical protocols and algorithms to facilitate decision-making for clinical assessment and management. It is aimed at nonspecialist health-care providers working at first-and second-level facilities. It is important that they are trained and then supervised and supported by specialists. The mhGAP-IG is also aimed for health care planners and programme managers in close conceptual and strategic synergy with the WHO's Comprehensive Mental Health Action Plan 2013-2020. The updated mhGAP guideline will be similarly incorporated into other mhGAP implementation materials.

# Dissemination plans
Relevant departments in Ministries of Health will be notified of the guideline through WHO Regional and Country Offices. A briefing package will be prepared for technical officers outside of WHO Headquarters that will include an executive summary and "Q&A" related to policy and programme implications. In particular, the briefing will highlight the new changes in the specific recommendations of the guideline.
Capacity building activities will be undertaken through regional and sub-regional meetings and other activities related to mhGAP and Comprehensive Mental Health Action Plan implementation.

# Supporting local adaptation and implementation
Local adaptation is necessary to ensure that the most burdensome conditions in a given country are covered and that the mhGAP guideline is appropriate for the local conditions that affect the care of people with MNS disorders. Adaptation includes language translation and ensuring that the interventions are acceptable in the local socio-cultural context and suitable for the local health system.
The implementation of the mhGAP guideline will also be supported locally through the adoption of the Comprehensive Mental Health Global Action Plan at country level. The national capacity building process will also be supported through collaboration with other partners such as other international organizations and civil society partners.

# Monitoring and evaluating quality of the guideline
After the publication of this guideline update, WHO will continue to collect regular feedback from implementation activities in order to evaluate its usefulness and impact. WHO will additionally continue to collect feedback from international experts and health care providers who are familiar with using the mhGAP guideline. This information will be used to evaluate the effects of the guideline on processes and health outcomes and to ensure the quality of the guideline and identify areas to be improved.

# Future review and update
The WHO Department of Mental Health and Substance Abuse will regularly monitor new evidence in these areas with the assistance of a WHO Collaborating Centre. The Department will also collect regular feedback from country implementation teams on mhGAP products, which are based on the mhGAP guideline.
After two years, literature searches will be carried out to check whether there are any major changes in the literature of any of the areas covered by the guideline. This will identify new potentially relevant evidence and enable us to assess whether the new information might have a significant effect on the recommendations. As two-yearly monitoring will need to be affordable and feasible in the long-term, this is not based on full literature reviews, but will consist of scoping searches of systematic reviews and other secondary products such as other evidence-based guidelines. Evidence profiles will be complemented with a short (up to one page) overview of how new evidence may affect the recommendation.
We plan to update the guideline again in five years using similar methodology to that of this second edition.

# List of Recommendations and Remarks
The recommendations for the mhGAP Guideline Update are provided below, including quality of evidence, strength of recommendation and remarks. These recommendations have been developed following the WHO Guideline Development process. Definition and description of interventions, together with the evidence retrieved and analysis of values and preferences and feasibility issues leading to these recommendations can be found in individual evidence profiles. These should be read in addition to the other relevant recommendations of the mhGAP guideline (available through the mhGAP Evidence Resource Centre: /).. They should keep in mind the possible adverse effects associated with antidepressant medications, the ability to deliver either intervention (in terms of expertise, and/or treatment availability), and individual preferences.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
Although the quality of the evidence is low to very low, the benefits of either intervention outweigh their harms with no differences between the interventions in direct comparisons. Indirect comparisons suggest that adverse effects are likely more pronounced with antidepressant medications.
Sufficient human resources (e.g., community health workers trained and supervised in delivering psychological treatment) and continuous medication supply need to be made available for psychological and antidepressant treatment, respectively.
Health care providers should discuss with help-seekers the pros and cons of either treatment (e.g. effects, including side effects, and time needed) allowing the person to decide which treatment he or she prefers.

# DEP2: Comparative effectiveness of different formats of psychological treatments for depressive disorder
Health care providers can offer different treatment formats of WHO's recommended, structured psychological interventions for adults and older adolescents with depressive disorder. These include behavioural activation, cognitive behavioural therapy (CBT), interpersonal psychotherapy (IPT), problem-solving treatment as an adjunct treatment (e.g. in combination with antidepressants). Different treatment formats for consideration include (a) individual and/or group face-to-face psychological treatments delivered by professionals and supervised lay therapists, as well as (b) self-help psychological treatment.
While face-to-face psychological treatment or guided self-help psychological treatment are likely to have better outcomes than unguided self-help, the latter may be suitable for those people who either (a) do not have access to face-to-face psychological treatment or guided self-help psychological treatment or (b) are not willing to access such treatments.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
There is low-quality evidence suggesting that the difference between individual and group treatment is small or non-existent. With respect to face-to-face versus self-help treatment, the research is more extensive, but the quality is very low. Overall there is substantial certainty in the value of expanding care through different means, and in the feasibility of expanding the delivery of psychological interventions beyond care by mental health professionals.
Choice of treatment format depends on social and health systems context.
WHO-recommended structured psychological treatments for depressive disorders in adults include: behavioural activation (BA), cognitive behavioural therapy (CBT) and interpersonal psychotherapy (IPT). In addition, existing WHO-recommended structured brief psychological treatments include problem-solving treatment as an adjunct treatment (e.g., in combination with antidepressants) for depressive disorder.
WHO recommended structured psychological treatments for emotional disorders in adolescents include: cognitive behavioural therapy, interpersonal psychotherapy, and caregiver skills training.
Self-help psychological treatment may involve information-technology (IT) supported self-help materials and paper-based self-help books.

# mhGAP Priority Condition: Psychosis (including schizophrenia and bipolar disorder)
PSY1: Role of depot antipsychotic medication in long-term antipsychotic treatment
In people with psychotic disorders (including schizophrenia) requiring long-term antipsychotic treatment, depot antipsychotics can be offered instead of oral medications as part of a treatment plan.

# Quality of Evidence: Very low

# Strength of recommendation: Conditional
Although the quality of the evidence is low to very low, the benefits of depot versus antipsychotics are similar in terms of hospitalizations and dropouts due to inefficacy. In terms of long-term relapse prevention, there is evidence that depot antipsychotics are significantly more effective than oral antipsychotics. The evidence also suggests that depot antipsychotics do not differ in terms of dropouts for adverse events when compared to oral preparations.
Patients and carers should be offered clear and accessible information in a suitable format regarding the use and possible side effects of oral versus depot preparations.

# PSY2: Antipsychotics and mood stabilizers (lithium, valproate, or carbamazepine) for maintenance treatment of bipolar disorder
Lithium or valproate or certain second-generation antipsychotics (aripiprazole, olanzapine, paliperidone extended release, quetiapine, and risperidone long acting injection release) can be offered for the maintenance treatment of bipolar disorder. If treatment with one of these agents is not feasible, first-generation antipsychotics or carbamazepine may be used. Maintenance treatment should be offered in primary health care settings under supervision of a specialist.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
Although there are concerns about safety and tolerability associated with long-term treatment with antipsychotics and mood stabilizers, there is low-quality evidence suggesting that the benefits of lithium, valproate and certain second-generation antipsychotics outweigh their harms. In terms of tolerability, both lithium and valproate have a narrow therapeutic index and can be toxic to multiple organ systems. A further important issue is the burden of taking mood stabilizers that requires regular blood monitoring.
Treatment with lithium should be initiated only in those settings where personnel and facilities for close clinical and laboratory monitoring are available.
All studies evaluating antipsychotic treatments have investigated the efficacy and tolerability profile of secondgeneration antipsychotics, while no direct evidence is available for first-generation antipsychotics. Evidence was considered for certain second-generation antipsychotics (aripiprazole, olanzapine, paliperidone extended release, quetiapine, and risperidone long acting injection release).

# PSY3: Recovery-oriented psychosocial strategies enhancing independent living and social skills (such as life skills and social skills training)
Recovery-oriented psychosocial interventions (e.g., life skills training, social skills training) to enhance independent living skills can be offered for people with psychotic disorders (including schizophrenia and bipolar disorder) and for their families and/or caregivers.
Facilitation of assisted living, independent living and supported housing that is culturally and contextually appropriate may be considered as an option for people with psychotic disorders (including schizophrenia and bipolar disorder). Careful consideration should be given to the functional capacity and the need for stability and support when advising and facilitating optimal housing arrangements.

# Quality of Evidence: Very low

# Strength of recommendation: Conditional
Randomized evidence supporting the efficacy of recovery-oriented psychosocial interventions is sparse and inconclusive. However, findings from a number of observational studies carried out in a very diverse range of settings suggest that benefits outweigh the harms. Overall there is substantial certainty in the value of psychosocial interventions, which may improve the social inclusion of people with psychotic disorders, as well as family members and caregivers, while reducing disability and preventing human rights violations.
Life skills training is a recovery oriented psychosocial intervention that emphasises the needs associated with independent functioning, and is usually part of the rehabilitation process. Social skills training is a recovery oriented psychosocial interventions included in illness management programs aimed at recovery.
Facilitation of assisted living and supported housing can act as a base from which people with severe mental disorders can achieve numerous recovery goals. Different housing strategies can be adopted depending on local resources and local cultural norms. Normal housing (single or shared, if acceptable to the user) or group living alternatives with appropriate support from a specialist may be crucial in promoting recovery in people with mental disorders.
Users, their families/caregivers and the community should be involved in the design, implementation and evaluation of these psychosocial interventions, in coordination with health and social professionals. Professionals delivering psychosocial interventions should have an appropriate level of competence and, wherever possible, be regularly supervised by the relevant specialists. Psychosocial interventions should be continued as long as needed by the user and his/her family and therefore should be planned and developed in a sustainable way.

# PSY4: Recovery-oriented strategies enhancing vocational and economic inclusion (such as supported employment)  Recommendation
Recovery-oriented strategies enhancing vocational and economic inclusion (e.g. supported employment) can be offered for people with psychosis (including schizophrenia and bipolar disorder). Such strategies should be contextualised to their social and cultural environment, using formal and non-formal recovery-oriented interventions that may be available, and using a multisectoral approach.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
Randomized evidence supporting the efficacy of recovery-oriented strategies enhancing vocational and economic inclusion is sparse and inconclusive. However, findings from a number of observational studies carried out in a very diverse range of settings suggest that benefits outweigh the harms. Overall there is substantial certainty in the value of recovery-oriented strategies enhancing vocational and economic inclusion, which may improve the social inclusion of people with psychotic disorders, as well as family members and caregivers, while reducing disability and preventing human rights violations.
Non-specialist health care providers should facilitate opportunities for people with psychosis and their families/caregivers to be included in economic activities in real world settings. Implementation of recoveryoriented psychosocial intervention programs requires a multisectoral approach such as collaboration with housing, employment, education and social sector.

# PSY5: Second-generation antipsychotic medications for psychotic disorders (including schizophrenia)  Recommendation
Second-generation antipsychotics (with the exception of clozapine which is indicated for treatment resistant psychosis) can be offered for the treatment of psychotic disorders (including schizophrenia). There is no clinically relevant advantage of one second-generation antipsychotic over others and choice should be based on availability, cost, patient preferences and possible adverse effects associated with each medication.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
Although the quality of the evidence is low, the benefits of second-generation antipsychotics outweigh their harms with no clinically relevant differences between individual interventions in direct comparisons. In the long-term, there are safety and tolerability concerns associated with antipsychotic treatment. A feasibility issue is the burden of taking medicines that require regular clinical and laboratory monitoring.
Although clozapine is more effective than other second-generation antipsychotics, its use is limited to patients that have not responded to other antipsychotics, as it may cause agranulocytosis. Regular blood tests during treatment are required to decrease this risk. Without monitoring, agranulocytosis occurs in about 1% of patients who take clozapine during the first few months of treatment.
The second generation antipsychotics considered in this evidence profile are aripiprazole, asenapine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, zotepine.
Possible adverse effects include sedation, metabolic, extrapyramidal, cardiovascular and hormonal side-effects.

# PSY6. Pharmacological interventions in adolescents with psychotic disorders
In adolescents with psychotic disorders (including schizophrenia and bipolar disorder) certain second-generation antipsychotic medications (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone) can be offered as a treatment option under supervision of a specialist.
If treatment with one of the above agents is not feasible, first-generation antipsychotics (haloperidol, chlorpromazine, perphenazine, molindone) may be used under supervision of a specialist.

# Quality of Evidence: Very low

# Strength of recommendation: Conditional
Although the quality of the evidence is very low, the benefits of certain second-generation antipsychotics outweigh their harms with no clinically relevant differences between individual interventions in direct comparisons. Some first-generation antipsychotics may be similarly effective in comparison with secondgeneration antipsychotics. In the long-term, there are relevant safety and tolerability concerns associated with antipsychotic treatment in this age group. A feasibility issue is the burden of taking medicines that require regular clinical and laboratory monitoring.
All studies in adolescents with psychotic disorders (including schizophrenia and bipolar disorder) have investigated the efficacy and tolerability profile of second generation antipsychotics, while no direct evidence is available for first-generation antipsychotics. However, comparisons of second-generation versus first-generation antipsychotics in adolescents and indirect evidence collected in adults with psychotic disorders (including schizophrenia and bipolar disorder) demonstrated the efficacy of first-generation antipsychotics.
Antipsychotic medications can give rise to adverse effects.
The evidence for the use of antipsychotics in adolescents is limited to specialist service settings and does not follow patients over long periods of time. It is for these reasons that supervision is required and that patients are monitored regularly for any incidence of unwanted side effects.
As there is no clinically relevant advantage of one antipsychotic over the others, choice should be based on availability, cost, preferences and possible negative consequences associated with each medication, including sedation, metabolic, extrapyramidal, cardiovascular and hormonal side-effects.

# mhGAP Priority Condition: Epilepsy

# EPI1: Anti-epileptic medications for management of acute convulsive seizures when no intravenous access is available  Recommendation
When intravenous access is not available for the control of acute seizures in adults, non-parenteral routes of benzodiazepine administrations should be used. Options include rectal diazepam, buccal or intranasal midazolam, rectal or intranasal lorazepam. The preference may be guided by availability, expertise and social preference. Some benzodiazepines (lorazepam or midazolam) may be given by intramuscular route, which requires additional expertise. Intramuscular administration of diazepam is not recommended because of erratic absorption.

# Quality of Evidence: Low

# Strength of recommendation: STRONG
A strong recommendation was made even with low quality evidence because the risk associated with not attempting to control seizures (e.g., sequelae of prolonged seizure or death) far outweighs any harms associated with using the interventions recommended. Although the quality of the evidence is low, there is no clinically important difference between non-intravenous routes of administration of benzodiazepines compared to intravenous routes for management of acute convulsive seizures. In a convulsing child or adult, establishing an intravenous access may be difficult; there may be lack of trained health care workers and lack of equipment in resource-limited settings. For patients and their families, non-intravenous treatment options may increase patient and family satisfaction. The availability of non-parenteral formulations of benzodiazepines may be a feasibility issue.
Relevant scenarios for using non-intravenous formulations may include community settings (pre-hospitalisation) or in a health care facility that is not equipped to administer intravenous medications or which does not have trained health care workers.
Intravenous formulations can be used for non-intravenous administration routes. If this should occur, particular caution should be taken with dosages to avoid administration errors.

# EPI2: First-line anti-epileptic medication for management of acute convulsive seizures, when intravenous access is available
In adults presenting with acute convulsive seizures where intravenous access is available, either intravenous lorazepam or diazepam can be administered to terminate the seizure. Intravenous lorazepam (if available) may be preferred over intravenous diazepam because of slightly superior benefit-risk profile.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
Although the quality of the evidence is low, the benefits of anti-epileptic medications outweigh their harms with intravenous lorazepam appearing to be more effective than intravenous diazepam for management of acute convulsive seizures in adults. Control of acute convulsive seizures is of critical importance as they are associated with substantial morbidity and mortality. Both intravenous lorazepam and diazepam are included in WHO Model Essential Medicine List.
Intravenous lorazepam may not be available in many low-and middle-income country settings.
In field settings, where the environmental temperatures are high and refrigeration is not available, intravenous diazepam may be preferable over lorazepam because of its better stability at higher environmental temperatures.
No recommendation can be made regarding intravenous midazolam, phenobarbital and phenytoin due to insufficient evidence.

# EPI3: Anti-epileptic medications for management of established status epilepticus
In adults with established status epilepticus, i.e. seizures persisting after two doses of benzodiazepines, either intravenous valproic acid, intravenous phenobarbital or intravenous phenytoin can be used with appropriate monitoring. Intravenous valproic acid is preferred over intravenous phenobarbital or intravenous phenytoin because of its superior risk-benefit profile. The choice of these medications depends on local resource settings, including availability and facilities for monitoring. Where intravenous infusion may not be feasible, intramuscular phenobarbital remains an option, with appropriate monitoring. Phenytoin and valproic acid should not be given intramuscularly.

# Quality of Evidence: Very low

# Strength of recommendation: Conditional
Status epilepticus is a medical emergency associated with substantial mortality and so its control is of critical importance. Although the quality of the evidence is very low, the benefits of intravenous phenytoin, phenobarbital and valproic acid outweigh their harms with no clinically relevant differences between individual interventions in direct comparisons in management of established status epilepticus. Advantages of valproic acid include lesser risk of cardiorespiratory side effects. Valproic acid is a broad-spectrum medication active against all types of seizures, and hence may be a good agent for maintenance therapy after the acute control of seizures in idiopathic generalized epilepsy or when the type of seizure/ epilepsy syndrome is not clear. However, valproic acid has the risk of hepatotoxicity and pancreatitis. Phenobarbital carries the risk of sedation and respiratory depression, which may be increased if it is used after benzodiazepines. Phenytoin carries the risk of arrhythmia and hypotension and difficulties in administration.
The above medications are initiated when seizures persist after two doses of benzodiazepines.
The choice of the medication can be affected by a number of factors, for example, the availability, cost and side effect profile of each.

# EPI4: Anti-epileptic medications for adults and children with HIV
In comparison with enzyme-inducing anti-epileptic medications (phenobarbital, phenytoin, carbamazepine) or valproic acid, newer generation anti-epileptic medications that are not hepatically metabolized (i.e. leviteracetam, lacosamide, topiramate, gabapentin and pregabalin) may be preferred to use in people with HIV on certain antiretroviral medications (protease inhibitors or non-nucleoside reverse-transcriptase inhibitors).
If the treatment with newer generation anti-epileptic medications is not feasible, valproic acid is preferred over the enzyme-inducing anti-epileptic medications (phenobarbital, phenytoin, and carbamazepine). In all cases, close monitoring of HIV viral load and regular clinical monitoring is required. If resources are available, anti-epileptic medication levels should be monitored.

# Quality of Evidence: Very low

# Strength of recommendation: Conditional
HIV and epilepsy comorbidity is common and presents a clinical challenge, thus in HIV-positive patients requiring antiepileptic medications and who are also on antiretroviral medications, the optimal choice must be considered based on the risk of drug-drug interactions and effects on HIV viral suppression. Although the quality of the evidence is very low, newer antiepileptic medications and valproic acid may provide useful alternatives to firstgeneration agents. A feasibility issue is that the newer antiepileptic medications are not on the WHO Essential Medicine List and so are more expensive. In addition, facilities for routine antiepileptic drug level monitoring are either not available or can be expensive in many countries.
Further research is needed in the following areas:
-Safety and efficacy of newer generation anti-epileptic medications (e.g., levetiracetam, lamotrigine, topiramate, pregabalin, and gabapentin) in patients on antiretroviral medications -Clinical adverse effects in patients on antiretrovirals and anti-epileptic medications -Further studies on the effects of hypoalbuminemia, hypergammaglobulenemia, and decreased gastrointestinal absorption on anti-epileptic medication levels in HIV-positive patients -Interaction studies and safety and efficacy studies in children on anti-epileptic medications and antiretrovirals

# EPI5: Anti-epileptic medicines for medication resistant convulsive epilepsy
Certain newer anti-epileptic medications (lamotrigine, levetiracetam and topiramate) should be offered as add-on therapy in patients with medication resistant convulsive epilepsy.
The essential anti-epileptic medications (carbamazepine, phenobarbital, phenytoin, and valproic acid) may be of benefit as add-on therapy in patients with medication resistant convulsive epilepsy.

# Quality of Evidence: Moderate
Strength of recommendation: Conditional
The balance of benefit versus harms is in favour of treatment with newer antiepileptic medications in medicationresistant convulsive epilepsy. The evidence for essential antiepileptic medications as an add-on therapy was based on observational studies. There were no head-to-head studies comparing the efficacy of the essential antiepileptic medications and the newer anti-epileptic medications of interest against each other for adults and children with medication resistant convulsive epilepsy. Despite the fact that anti-epileptic medications are associated with some adverse events, most people with medication-resistant convulsive epilepsy would choose to be on these medications to decrease the risk of morbidity and mortality. The newer antiepileptic medications are not on the WHO Essential Medicines List and so cost may prove a barrier to use in low-resource settings.
Medication selection should also be appropriate based on the type of epilepsy as some anti-epileptic medications can worsen generalized convulsive seizures (e.g., carbamazepine, phenytoin and phenobarbital should be avoided in patients with myoclonic epilepsy). Patients' comorbidities and childbearing potential also have to be considered when recommending a newer antiepileptic medication in those with medication resistant convulsive epilepsy as some antiepileptic medications are associated with a higher risk of teratogenicity and worst neurodevelopmental outcomes than others (e.g., valproic acid), or could worsen comorbid conditions (e.g., depression, obesity, etc.).

# mhGAP Priority Condition: Mental disorders with childhood onset CH1: Caregiver skills training for management of developmental disorders
Caregiver skills training should be provided for management of children and adolescents with developmental disorders, including intellectual disabilities and pervasive developmental disorders (including autism).

# Quality of Evidence: Low

# Strength of recommendation: Strong
A strong recommendation was made even with low quality evidence based on the benefits outweighing harms and the values and preferences indicating that children and adolescents with intellectual disabilities or pervasive developmental disorders have the right to a supportive and understanding family environment. Low-quality evidence suggests that caregiver skills training is associated with better outcomes in child development and reductions in problem behaviours. It is generally agreed that it is important for caregivers to acquire skills to better enable and support the development, functioning and participation of children with developmental disorders. In terms of feasibility, evidence supports the notion that training for caregivers of children and adolescents with intellectual disabilities and pervasive developmental disorders can be effectively delivered by non-specialists in community settings.
Caregiver skills training should use culturally appropriate training material relevant for those disorders to improve development, functioning, and participation of the children and adolescents within families and communities.
Health-care providers need additional training to be able to offer caregiver skills training.
Training and education of caregivers and other family members could ensure that children with intellectual disabilities or pervasive developmental disorders are given the dignity and opportunities that they are entitled to.

# CH2: Psychosocial interventions for treatment of behavioural disorders
Behavioural interventions for children and adolescents, and caregiver skills training, may be offered for the treatment of behavioural disorders.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
The available evidence indicates that caregiver skills training and behavioural interventions for the patients can reduce symptoms for children with behavioural disorders and improve family and caregiver functioning. Additionally, behavioural and cognitive behavioural interventions can be effective in improving school performance. There were no adverse outcomes reported, in terms of additional psychological or familial burdens associated with participation in these interventions. There is value of intervening early to reduce adverse outcomes associated with behavioural disorders.
The choice of behavioural intervention (eg. behavioural and cognitive behavioural therapies, school-based therapies, and caregiver skills training), and how it is implemented should be based on the type of behavioural disorder(s) and the age and developmental stage of the child or adolescent. The child or adolescent's family should be involved in the intervention whenever appropriate. The content should be culturally sensitive and should not allow violation of the child or adolescent's basic human rights according to internationally endorsed principles.
The social environment, family context and other psychosocial and physical risk factors that may be contributing to or exacerbating the behaviour disorder should be considered and addressed, whenever possible.
Health care providers should be aware that behavioural problems may be an expression of underlying emotional problem(s)/disorder(s).

# CH3: Psychosocial interventions for treatment of emotional disorders
Psychological interventions, such as cognitive behavioural therapy (CBT), interpersonal psychotherapy (IPT) for children and adolescents with emotional disorders, and caregiver skills training focused on their caregivers, may be offered for the treatment of emotional disorders.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
For children with emotional disorders, there is low quality evidence that behavioural and cognitive behavioural interventions can lead to symptom reduction and disorder remission. There were no adverse outcomes reported, in terms of additional psychological or familial burdens associated with participation in these interventions.
Feasibility depends on local resources, as well as the choice and format of the psychosocial treatment offered.
The choice of psychological intervention and how it is implemented should be based on the type of emotional problem(s) and the age and developmental stage of the child or adolescent. The child or adolescent's family should be involved in the intervention, whenever appropriate. The content should be culturally sensitive and should not allow violation of the child or adolescent's basic human rights according to internationally endorsed principles.
The social environment, family context, and other psychosocial and physical risk factors that may be contributing to or exacerbating the emotional disorder should be considered and addressed.

# CH4: Antidepressants among adolescents with moderate-severe depressive disorder for whom psychosocial interventions have proven ineffective
When psychosocial interventions prove ineffective, fluoxetine (but not other Selective Serotonin Reuptake Inhibitors or Tricyclic Antidepressants) may be offered in adolescents with moderate-severe depressive episode/disorder. The intervention should only be offered under supervision of a specialist.

# Quality of Evidence: Very low

# Strength of recommendation: Conditional
Although in the long-term there are safety and tolerability concerns associated with antidepressant treatment in this age group, the evidence suggests that fluoxetine is an SSRI with a favourable benefit to risk ratio. Clinicians need to be trained in prescribing antidepressants, including side-effects monitoring.
Within the context of this recommendation, specialists include (a) psychiatrists and neuro-psychiatrists (b) paediatricians and family physicians with post-degree training in the management of adolescent depression.
The decision to prescribe fluoxetine should be made together with the adolescent in line with the evolving capacity of the adolescent.
Adolescents on fluoxetine should be monitored closely for suicide ideas/behaviour.
Fluoxetine treatment should not be started with greater than minimal effective doses. It is suggested to initiate treatment with 10 mg once daily and increase to 20 mg after 1 -2 weeks (maximum dose 20 mg). If no response in -12 weeks or partial response in 12 weeks, re-consult a specialist.
In countries that only have 20mg capsules that cannot be split in half, due to the long half-life of fluoxetine, it is possible to prescribe fluoxetine 20mg every other day (equivalent to initial dose of 10mg/day).

# CH5: Effective strategies for detecting maltreatment of children and youth within the context of mental health and developmental assessment
Health care providers should be alert to the clinical features associated with child maltreatment and associated risk factors and assess for child maltreatment, without putting the child at increased risk.

# Quality of Evidence: Very low

# Strength of recommendation: Conditional
Evidence supporting the efficacy of strategies for detecting maltreatment of children and youth within the context of mental health and developmental assessment is sparse and inconclusive. No studies have evaluated the performance of measures in predicting referrals and health outcomes. However, it is generally agreed that it is important for health care providers to detect child maltreatment. It is recognised that assessment of child maltreatment requires a clinician who is competent enough to ask the right questions and to respond appropriately.
Inquiry into child maltreatment should occur in the context of case finding and diagnostic assessment by clinicians competent to do so and should be followed by interventions, referral and/or follow up. Inquiry and following actions should take into account the availability of interventions, such as caregiver skills training, and services.
There is no evidence to support universal screening or routine inquiry.
The strategies, including reporting and follow-up of the assessment should be culturally sensitive and should not allow violation of children's basic human rights according to internationally endorsed principles.
Examples of child maltreatment include physical abuse, sexual abuse, neglect, emotional abuse and all other forms of child maltreatment.

# CH6: Community-based rehabilitation for adults with developmental disorders including intellectual disabilities and autism spectrum disorders
Non-specialized health care providers can offer supporting, collaborating and facilitating referral to and from community based rehabilitation (CBR) programmes, if available, for care of adults with developmental disorders, including intellectual disabilities and pervasive developmental disorders (including autism).

# Quality of Evidence: Very low

# Strength of recommendation: Conditional
Evidence supporting the efficacy of community-based rehabilitation for adults with developmental disorders is sparse and inconclusive. The provision of psychosocial rehabilitation is in line with internationally endorsed principles on the rights of people with disabilities.
Intervention programmes should be developed and adapted taking into consideration the sociocultural context and with involvement of program users.

# mhGAP Priority Condition: Dementia

# DEM1: Cholinesterase inhibitors and memantine for treatment of dementia
Cholinesterase inhibitors and memantine may be offered to people with dementia in non-specialist health settings. Non-specialists need to be trained and supervised to ensure competence in diagnosis and monitoring.
The use of cholinesterase inhibitors should be focused upon those with mild to moderate Alzheimer's disease, where the majority of evidence is available.
Memantine may be considered for those with moderate to severe Alzheimer's disease and vascular dementia. Memantine should not be prescribed for Lewy Body dementia.

# Quality of Evidence: Very low

# Strength of recommendation: Conditional
Cholinesterase inhibitors and memantine offer symptomatic benefits in cognitive, functional, global and behavioural outcomes, although the size of this benefit is uncertain and the quality of the evidence very low. Adverse effects and safety in the long-term may represent serious concerns. Dementia diagnosis and subtype definition and management with the above medications require training, supervision and support. Moreover these medications are associated with high acquisition costs.
Consideration should be given to adherence and monitoring of adverse effects.

# DEM2: Psychological therapies for people with dementia who have associated depression
People with dementia and mild to moderate symptoms of depression may be offered psychological interventions (such as cognitive behavioural therapy interpersonal therapy structured counselling and behavioural activation therapy), in non-specialized health care settings under supervision of a specialist.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
Depression is common among people with dementia and is associated with significant adverse effects, including decrease in quality of life, increased need for institutionalization, greater health care utilization, higher mortality rates and increased caregiver burden. There is limited low quality evidence that the use of psychological treatments may reduce symptoms of depression in this population. Delivery of these interventions require adequate training and supervision of non-specialist health care provider.
Psychological interventions may not be feasible as a treatment for people with severe dementia and symptoms of depression due to impaired cognitive function.
It is possible to train non-specialist health care workers to provide psychological treatments with the close supervision of a specialist.
None of the primary studies available on psychological interventions were carried out in low-or middle-income countries.
The type of psychosocial intervention offered should be based upon the capacity of health care workers and patient preferences.

# DEM3: Pharmacological interventions (antidepressants) for people with dementia who have associated depression
In people with dementia and severe depression, or when psychosocial interventions prove ineffective, the use of selective serotonin reuptake inhibitors (SSRIs) (but not tricyclic antidepressants may be considered.
In people with dementia and mild to moderate depression, antidepressants should not be offered as a first-line treatment.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
The evidence to support the use of antidepressants for the treatment of comorbid depression in dementia is inconclusive. Clinicians must be vigilant regarding the potential side-effects of antidepressants in this population, especially tricyclic antidepressants, as they are associated with side-effects that are potentially more problematic for elderly patients.
This evidence implies a need to change current practice of antidepressants being the first-line treatment of depression in individuals with dementia.
Tricyclic antidepressants (TCAs) are associated with more adverse effects than are selective serotonin reuptake inhibitors (SSRIs) in older adults.

# DEM4: Oral nutrition supplementation or dietary education for caregivers for managing people with dementia at risk of undernutrition or currently undernourished
In people with dementia who are at risk of undernutrition, dietary advice aimed at food fortification should be tried first, and weight and nutritional status monitored. If nutritional status is not improved, then oral nutritional supplementation should be used (in the absence of any clinical contraindication) to achieve weight gain and restore nutritional status.

# Quality of Evidence: Low
Strength of recommendation: STRONG
Undernutrition is common among people with dementia and is associated with significant adverse effects, including more rapid clinical progression and cognitive decline, hospitalization, falls and death. There is evidence that the use of oral nutritional supplementation is efficacious in attaining clinically significant weight gain in people with dementia who are undernourished or at risk of undernutrition, although the quality of the evidence is low. However oral nutritional supplementation is generally well tolerated among people with dementia and there is no evidence of any significant harms. Caregiver anxiety over their inability to achieve adequate nutrition and to stabilize the weight of the cared-for-person with dementia is a significant source of caregiver strain. A strong recommendation was made even with low quality evidence because the risk and negative health effects of malnutrition are serious and outweigh any harm that could be associated with the recommended treatment.
People with dementia should be regularly assessed for weight loss and nutritional status. For those who are found to be undernourished or at risk of undernutrition, an assessment should be carried out for general health status, dietary habits, and for the presence of any adverse feeding behaviours. Suspicion of serious underlying physical disease should trigger an urgent referral for medical assessment.

# DEM5: Nutritional interventions for people with dementia or cognitive impairment
In people with either cognitive impairment or dementia, supplementation with nutrients, or use of Gingko biloba extracts should not be considered to improve cognitive function, to reduce the risk of developing dementia or to slow the progression of dementia once established.
When feasible, dietary deficiencies should be investigated and monitored in those with dementia and appropriate supplementations should be provided.
Current evidence does not suggest any benefit in people with dementia or those with cognitive impairment, with micronutrient supplementation (vitamin B complex, vitamin E, Omega-3) or Ginkgo biloba extract or Mediterranean diet, the quality of evidence is very low and at present this should be considered inconclusive.
None of the primary studies available have been carried out in low-and middle-income countries. Moreover, very few randomized controlled trials to date on supplementation have been carried out in the patient groups who are deficient in the relevant micronutrient.
Vitamin E supplementation in those with dementia and adherence to a Mediterranean diet in cognitively healthy older adults may have some potential benefits on cognitive function: however, further research is required.
Baclofen can be offered to prevent relapse among people with alcohol dependence post-detoxification.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
There is short-term evidence suggesting that baclofen improves abstinence from alcohol compared to placebo. There were no serious side effects reported; however, baclofen can cause sedation and cessation of baclofen can be associated with a mild benzodiazepine-like withdrawal syndrome. Patients value affordable and available treatments for alcohol dependence. Baclofen is available in generic form and is inexpensive. Baclofen may not available in all countries and is not registered for the use of alcohol dependence.
A dose of 10mg three times a day is recommended initially, but can be increased to 20mg three times a day if needed.
Baclofen should be reduced gradually rather than stopped abruptly because of the risk of a mild benzodiazepine withdrawal-like syndrome.

# ALC2: Psychosocial interventions for the management of alcohol dependence
Recommendation ALC 2: Psychosocial interventions including cognitive behavioural therapy (CBT), couples therapy, psychodynamic therapy, behavioural therapies, social network therapy, contingency management and motivational interventions, and twelve-step facilitation can be offered for the treatment of alcohol dependence.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
Although the quality of the evidence is low, the benefits of psychosocial interventions outweigh their harms for the management of alcohol dependence. Alcohol dependence produces significant distress and decreased functioning. In terms of managing alcohol dependence people would value being able about their alcohol use and related psychological and social problems. They would also value being abstinent and reducing their drinking.
The list above contains those examples of structured psychosocial support that have been shown to be effective. Given the nature of psychosocial support and the limited number of countries in which the psychosocial support has been tested, it may be useful to introduce measures to routinely monitor the effectiveness of treatment, such as the retention rate and the rates of drug use in treatment, in order to know that that the treatment provided is effective.
Non-specialist health care providers require training in and supervision for delivery of psychosocial interventions.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
Although the quality of the evidence is low, the benefits of psychosocial interventions outweigh their harms with no clinically relevant differences between individual interventions in direct comparisons. Cannabis disorders can produce significant distress and decreased functioning among some individuals. In terms of managing cannabis dependence, people would positively value being able to talk about their drug use and related psychological and social problems.
There may also be a role for family interventions, group interventions, and 12 step interventions.
Other forms of psychosocial support may be effective, but the evidence for this is lacking at this stage.
Non-specialist health care providers require training in and supervision for delivery of psychosocial interventions.

# DRU2: Psychosocial interventions for the management of psychostimulant dependence
Recommendation Psychosocial interventions including contingency management, cognitive behavioural therapy (CBT) and family therapy can be offered for the treatment of psychostimulant dependence.

# Quality of Evidence: Very low

# Strength of recommendation: Conditional
Although the quality of the evidence is very low, the benefits of psychosocial interventions outweigh their harms. Generally, there is belief that people would value being able to talk to others about their drug use and related psychological and social problems, however some value their privacy more. Non-specialist health care providers require training in and supervision for delivery of psychosocial interventions.
Although many of the research trials use monetary reinforcement, use of contingency management should be adapted to the culture and population with input from patients.
DRU3: Supervised dosing with a long acting opioid medication for the management of prescription opioid dependence
When managing people who are dependent on strong prescription opioids (i.e. morphine-like), physicians can switch to a long acting opioid (such as methadone and buprenorphine) which can be taken once daily, with supervised dispensing if necessary, either for maintenance treatment or for detoxification.

# Quality of Evidence: Low

# Strength of recommendation: Conditional
There is low quality evidence regarding the benefits of long acting opioid medication for the management of prescription opioid dependence. However both buprenorphine and methadone are medications that can be diverted from treatment to illicit sales, which is a cause for concern. Maintenance treatment might be the preferred option for patients who find it difficult to cease opioids, either because of pain recurrence or opioid dependence symptoms. In some countries, neither buprenorphine nor methadone are available and maintenance treatment is not possible due to supply chain issues. National legislation surrounding controlled drugs can also negatively impact availability.
The prescription of long acting opioids such as methadone and buprenorphine in the maintenance treatment of opioid dependence is most safely conducted following specific training, or under the supervision of a specialist in the treatment of opioid dependence. Within the category of "supervised long acting opioid medication", which includes methadone, buprenorphine and slow-release oral morphine, buprenorphine has most evidence of support and has a variety of advantages, including lower overdose risk and better harms profile. However, methadone can be another option, when buprenorphine is not available. If methadone and buprenorphine treatment are not available, it may be possible to substitute methadone and buprenorphine with another long acting opioid which is available and to supervise the dispensing daily if necessary.
When deciding between maintenance and detoxification options, the duration and severity of the opioid dependence, past history of illicit drug use, and patient preference should be taken into consideration.
Patients should be advised that people with opioid dependence who detox are at a higher risk of overdose having completed detoxification, as their tolerance to opioids will have dropped.
The duration of maintenance treatment is difficult to determine, but generally, the patient should not be encouraged to cease maintenance treatment until they have ceased other substance use.
For detoxification, it may be preferable to titrate the pace of reduction to the patients' capacity to manage the opioid withdrawal symptoms.
The implementation of suicide prevention programmes in school settings that include mental health awareness training and skills training can be offered to reduce suicide attempts and suicide deaths among adolescent students.

# Quality of Evidence: Low
Strength of recommendation: Conditional
Mental health awareness programmes that include skills training (e.g., problem solving, coping with stress) have been found to be effective in reducing suicide attempts, although the quality of the evidence is low. Potential harms may result through a lack of healthcare and community resources to provide care for at-risk adolescents who seek help.
Most of the described interventions have been administered and evaluated in adolescent populations of 14-17 years old.
Suicide prevention programmes, including the training of programme providers, would need to be adapted/contextualized to local religious, cultural and legal settings in a sensitive and appropriate manner. The declaration of interest forms submitted by the mhGAP Guideline Development Group (GDG) was reviewed. An interest has been declared by the experts mentioned below and their significance and assessment is indicated after consultation with the Director of the Department.
- Robert Ali -The declared interest was assessed to be significant but relates only to one areas of the GDG's work -(i.e., opioid substitution treatment). It was proposed that the said experts is excluded from the decision making process related to the guideline key question relevant to the area of opioid substitution (partial exclusion). Please note that the said expert did not participate in the GDG meeting 3-5 December 2014. After consultation with the Chair of GDG, the reported interest was publically disclosed to other meeting participants and was recorded and will be disclosed in the report of the meeting and/or relevant publications. 2. Vladimir Carli -It was assessed that the declared interest was insignificant or minimal as it was only tangentially related to the subject of the work under consideration. 3. Sudipto Chatterjee -It was assessed that the declared interest was insignificant or minimal as it was only tangentially related to the subject of the work under consideration. 4. Julian Eaton -It was assessed that the declared interest was insignificant or minimal as it was only tangentially related to the subject of the work under consideration. 5. Atif Rahman -It was assessed that the declared interest was insignificant or minimal as it was only tangentially related to the subject of the work under consideration. 6. Richard Rawson -The declared interest was assessed to be potentially significant, as the nature of the interest is mostly research funding from federal agencies (with some amount from philanthropic foundation). We proposed conditional participation of the said expert. After consultation with the Chair of GDG, the reported interest was publically disclosed to other meeting participants and was recorded and disclosed in the report of the meeting and/or relevant publications. 7. Pratap Sharan -The declared interest was assessed to be not relevant to the area under consideration. 8. Graham Thornicroft -It was assessed that the declared interest was insignificant or minimal as it was only tangentially related to the subject of the work under consideration. (2) Systematic reviews; and (3) Individual studies which were searched if systematic reviews were not available and/or depending on the PICO question.
Methods to detect the possibility of publication bias in systematic reviews exist, although authors of the reviews and guideline panels must often guess about the likelihood of publication bias. A prototypical situation that should elicit suspicion of publication bias occurs when published evidence is limited to a small number of trials, all of which are showing benefits of the studied intervention.
The following criteria will be followed by WHO raters on REPORTING BIAS:
If the graphical inspection of the funnel plot suggests some asymmetry, or if any other reasons (to be recorded as footnote) suggest that reporting bias might have had an impact on the overall summary estimate (for example: unpublished grey literature was not included) = - 1If the graphical inspection of the funnel plot suggests high asymmetry, or if any other reasons (to be recorded as footnote) suggest that reporting bias might have had a high impact on the overall summary estimate (for example: unpublished grey literature was not included) = -2 A different criterion may be followed by WHO raters in exceptional situations. Explanation should be reported as footnote in the corresponding GRADE table.

# Upgrading the evidence
Please note that the randomized trials downgraded for any reason, can't be upgraded.

# (6) DOSE-RESPONSE GRADIENT
PLEASE NOTE: The dose-response gradient is assessed only in observational studies not downgraded for any reason.
The presence of a dose-response gradient may increase our confidence in the findings of observational studies and thereby increase the quality of evidence. Only observational studies with no threats to validity (not downgraded for any reason) can be upgraded.

# (7) LARGE MAGNITUDE OF EFFECT
You should assess if the effect was large or very large and, if so, upgrade the quality of evidence accordingly for this outcome. For observational studies, only studies with no important threats to validity (not downgraded for any reasons) can be upgraded.
To rate magnitude of the effect:  If the effect was not large (RR between 0.5 and 2.0) choose no  If the effect was large (RR either >2.0 or 2 or 5.0 or 5 or <0.2 this will upgrade the quality of evidence for this outcome by 2 levels  Explain your choice in a footnote whenever you upgrade the quality of evidence for any reason, because it is important for others to understand the rationale for your choice.

# (8) EFFECT OF ALL PLAUSIBLE CONFOUNDING
On occasion, all plausible confounding may be working to reduce the demonstrated effect or increase the effect if no effect was observed.
For example, if only sicker patients receive an experimental intervention or exposure, yet they still fare better, it is likely that the actual intervention or exposure effect is larger than the data suggest. For observational studies, only studies with no important threats to validity (not downgraded for any reasons) can be upgraded.