Results of a naturalistic longitudinal study of benzodiazepine and SSRI use in the treatment of generalized anxiety disorder and social phobia. Use of benzodiazepines and selective serotonin reuptake inhibitors in middle-aged and older adults with anxiety disorders: a longitudinal and prospective study. The diagnosis and treatment of generalized anxiety disorder. The selective serotonin reuptake inhibitor paroxetine is effective in more generalized and in less generalized social anxiety disorder Nefazodone in the treatment of generalized social phobia: a randomized, placebo-controlled trial. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders – First Revision Psychopharmacological treatment of social phobia; a double blind placebo controlled study with fluvoxamine Paroxetine treatment of generalized social phobia (social anxiety disorder): a randomized controlled trial. A pragmatic 12-week, randomized trial of duloxetine versus generic selective serotonin-reuptake inhibitors in the treatment of adult outpatients in a moderate-to-severe depressive episode Fluvoxamine treatment of social phobia (social anxiety disorder): a double-blind, placebo-controlled study. An open trial of topiramate in the treatment of generalized social phobia. Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study. Reboxetine, a selective norepinephrine reuptake inhibitor, is an effective and well-tolerated treatment for panic disorder. Efficacy of citalopram and moclobemide in patients with social phobia: some preliminary findings. Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians The expert consensus guideline series. Treatment of dementia and its behavioral disturbances. Introduction: methods, commentary, and summary. A Review of Vilazodone, Serotonin, and Major Depressive Disorder Fluoxetine in Social Phobia: A Double-Blind, Placebo-Controlled Pilot Study Guidelines for the pharmacological treatment of anxiety disorders, obsessive–compulsive disorder and posttraumatic stress disorder in primary care Quetiapine augmentation of serotonin reuptake inhibitors in obsessive-compulsive disorder A Double-Blind, Placebo-Controlled Study of a Flexible Dose of Venlafaxine ER in Adult Outpatients With Generalized Social Anxiety Disorder Are benzodiazepines still the medication of choice for patients with panic disorder with or without agoraphobia? Strategy for treating selective serotonin reuptake inhibitor-resistant social anxiety disorder in the clinical setting: a randomised controlled trial protocol of cognitive behavioural therapy in combination with conventional treatment
The past decade has brought major new developments in the psychopharmacologic management of generalized anxiety disorder and social phobia . We examined medication-prescribing patterns for the treatment of these anxiety disorders for 12 years to assess changes in patients ' anti-anxiety psychotropic medication usage during that period of evolving practice guidelines . We examined psychotropic medication use in 305 patients with generalized anxiety disorder and 232 with social phobia enrolled in the Harvard/Brown Anxiety Disorders Research Project ( HARP ) , a prospect i ve , longitudinal study of anxiety disorders .  Psychotropic treatment patterns seem to have remained relatively stable over 12 years with benzodiazepines the medications most commonly used for both generalized anxiety disorder and social phobia . Comparatively , selective serotonin reuptake inhibitor ( SSRI ) and venlafaxine usage as st and -alone medications for these disorders remained low throughout the follow-up period . At the 12-year follow-up , 24 % of patients with generalized anxiety disorder and 30 % of patients with social phobia were utilizing neither an  SSRI/selective norepinephrine reuptake inhibitor ( SNRI ) nor a benzodiazepine . Treatment recommendations for use of SSRIs and venlafaxine in the management of generalized anxiety disorder and social phobia initially promulgated in 1998 had a modest impact on changes in psychopharmacologic practice 4 - 5 years later . Difficulties in the implementation of treatment guidelines are discussed OBJECTIVE The purpose of this study was to examine the use of benzodiazepines ( BZs ) and selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors ( SSRIs/SNRIs ) over nine years of follow-up in middle-aged and older adults with diagnoses of panic disorder with or without agoraphobia , social phobia , or generalized anxiety disorder . SETTING AND PARTICIPANTS Participants in this study were enrolled in the Harvard/Brown Anxiety Research Project ( HARP ) . HARP is a naturalistic , longitudinal , multisite study of adults with anxiety disorders who are recruited from psychiatric setting s. The analytic sample consisted of 51 participants with anxiety disorders who were 55 to 70 years old at baseline and a younger cohort of 211 participants added for comparative analysis . DESIGN The authors examined patterns of medication use ( BZs and SSRIs/SNRIs ) in participants with anxiety disorders as they aged , by assessing the proportion of participants taking these medications using generalized estimating equation modeling . MEASUREMENTS The present data were derived from the structured diagnostic interview administered at enrollment using a combination of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders , Third Edition-R Non-Affective Disorder , Patient Version , Research Diagnostic Criteria Schedule for Affective Disorders-Lifetime , and subsequent follow-up interviews over a nine-year period using the Longitudinal Interval Follow-up Evaluation-Pharmacia & Upjohn to assess the weekly course of disorders to indicate syndrome severity and document medication use by specific type and dose on a weekly basis . RESULTS Findings showed that rates of BZ use were high among both the older ( 53 % at baseline ) and the younger ( 57.4 % ) age groups and did not significantly decrease over time , after controlling for time in episode of their anxiety disorders . There was a statistically significant increase in  SSRI/SNRI use over time in both groups . At the beginning of the study , 18 % of the older group and 21 % of the younger group were using SSRIs/SNRIs ; however , at the end of the study , the rates increased to 35 % and 43 % , respectively . CONCLUSIONS Although there was an increase in  SSRI/SNRI use in older participants with anxiety disorders over the course of study , at nine years of follow-up , only 35 % of participants were utilizing SSRI/SNRI medication , while more than one-half of the same participants were continuing to use BZs . To the authors ' knowledge , there are no r and omized clinical trials that have addressed comparative efficacy and safety of BZs and SSRIs/SNRIs in this population . However , there is documented evidence of adverse effects of chronic BZ use and the risk of developing dependency in older population BACKGROUND Generalized anxiety disorder  ( GAD ) is a common and serious disease with a lifetime prevalence of 4.3 % to 5.9 % . It is underdiagnosed in primary care . METHODS Recommendations on the treatment of GAD are given on the basis of all available findings from pertinent r and omized trials , retrieved by a selective search of the literature . RESULTS Among psychotherapeutic techniques , various kinds of cognitive behavioral therapy ( CBT ) have been found useful in controlled trials . The drugs of first choice include selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-norepinephine reuptake inhibitors ( SNRIs ) , and the calcium-channel modulator pregabalin . Tricyclic antidepressants are also effective but have more adverse effects than SSRIs . Although benzodiazepines are effective anxiolytic agents for short-term use , they should not be given over the long term because of the danger of addiction . Buspirone , an azapirone , was found to be effective in a small number of trials , but the findings across trials are inconsistent . The response rate of GAD to CBT in published studies lies between 47 % and 75 % , while its response rate to drug treatment lies between 44 % and 81 % . CONCLUSION The treatment of GAD with CBT and drugs is evidence -based and has a good chance of improving the manifestations of the disorder Abstract . Rationale : The DSM-IV includes the specifier " generalized " to refer to social anxiety disorder ( social phobia ) patients if the fears include " most social situations " . The focus on interventions such as the selective serotonin reuptake inhibitors ( SSRIs ) for generalized social anxiety disorder arguably runs the risk that inadequate treatment will be provided to patients with the non-generalized or discrete subtypes . There are , however , few data to address whether more generalized and less generalized subgroups of social anxiety disorder differ in response to medication . Objective : To compare response of more generalized and less generalized social anxiety disorder to pharmacotherapy . Methods : Data from three r and omized placebo-controlled double-blind multicenter trials of the SSRI paroxetine in social anxiety disorder were pooled . Response on the Clinical Global Impression Global Improvement item was analyzed using logistic regression , and change in total Liebowitz Social Anxiety Score was analyzed using analysis of variance , with both models incorporating treatment ( paroxetine vs placebo ) , subgroup ( more generalized vs less generalized ) , demographic , and clinical variables . Results : The prevalence of more generalized social anxiety disorder was higher in females than in males . However , there was no significant difference in terms of age or clinical characteristics ( duration of condition , baseline pulse , mean arterial blood pressure ) . At treatment endpoint there were significant treatment effects ( for paroxetine vs placebo ) , but no significant subgroup effects ( for more generalized vs less generalized ) . Conclusions : Although the current data base is limited insofar as few patients with discrete social anxiety disorder would have been included , it is helpful in addressing the value of medication for patients lying on the spectrum from generalized to non-generalized and discrete social anxiety disorder .  Paroxetine was effective in both more generalized and in less generalized social anxiety disorder OBJECTIVE Numerous studies have demonstrated the efficacy of serotonergic antidepres-sants , particularly the selective serotonin reuptake inhibitors ( SSRIs ) , in the treatment of social phobia . We evaluated the efficacy , safety , and tolerability of nefazodone , a 5-HT(2 ) antagonist , in patients with generalized social phobia ( GSP ) . METHOD One hundred five patients with GSP ( confirmed using the Structured Clinical Interview for DSM-IV ) from 4 Canadian outpatient anxiety clinics were assigned r and omly to nefazodone ( 300 - 600 mg/day , flexible dose ) or placebo for 14 weeks of double-blind treatment . Data were collected from October 12 , 1999 , through December 8 , 2001 . Primary efficacy outcomes were the Clinical Global Impressions-Improvement scale ( CGI-I ) score and the Liebowitz Social Anxiety Scale score . RESULTS In the intent-to-treat sample , 16 ( 31.4 % ) of 51 subjects taking nefazodone and 12 ( 23.5 % ) of 51 subjects taking placebo were rated as much or very much improved on the CGI-I at endpoint ( chi(2 ) = 0.79 , p = .38 ) . With the exception of the Social Phobia Scale , no significant differences were found in measures of social phobia when comparing the nefazodone and placebo groups . CONCLUSION These findings suggest that nefazodone is not an effective agent in the treatment of GSP . These data parallel some recent findings with the use of the SSRI fluoxetine in GSP . The lack of efficacy of 2 serotonergic antidepressants in GSP suggests that serotonin reuptake inhibition may not be the only mechanism of action required for efficacy to occur in the treatment of GSP In this report , which is an up date of a guideline published in 2002 ( B and elow et al. 2002 , World J Biol Psychiatry 3:171 ) , recommendations for the pharmacological treatment of anxiety disorder , obsessive-compulsive disorder ( OCD ) and post-traumatic stress disorder ( PTSD ) are presented . Since the publication of the first version of this guideline , a substantial number of new r and omized controlled studies of anxiolytics have been published . In particular , more relapse prevention studies are now available that show sustained efficacy of anxiolytic drugs . The recommendations , developed by the World Federation of Societies of Biological Psychiatry ( WFSBP ) Task Force for the Pharmacological Treatment of Anxiety , Obsessive-Compulsive and Post-traumatic Stress Disorders , a consensus panel of 30 international experts , are now based on 510 published r and omized , placebo- or comparator-controlled clinical studies ( RCTs ) and 130 open studies and case reports . First-line treatments for these disorders are selective serotonin reuptake inhibitors ( SSRIs ) , serotonin-noradrenaline reuptake inhibitors ( SNRIs ) and the calcium channel modulator pregabalin . Tricyclic antidepressants ( TCAs ) are equally effective for some disorders , but many are less well tolerated than the SSRIs/SNRIs . In treatment-resistant cases , benzodiazepines may be used when the patient does not have a history of substance abuse disorders . Potential treatment options for patients unresponsive to st and ard treatments are described in this overview . Although these guidelines focus on medications , non-pharmacological were also considered . Cognitive behavioural therapy ( CBT ) and other variants of behaviour therapy have been sufficiently investigated in controlled studies in patients with anxiety disorders , OCD , and PTSD to support them being recommended either alone or in combination with the above medicines Previous studies have shown selective and non-selective monoamine oxidase inhibitors ( MAOIs ) to be effective in the treatment of social phobia . In this study we investigated the efficacy of selective serotonin reuptake inhibitors ( SSRIs ) in social phobia . Thirty patients with social phobia ( DSM-IIIR ) were treated with the SSRI fluvoxamine ( 150 mg daily ) using a 12-week double-blind placebo controlled design . A substantial improvement was observed in seven ( 46 % ) patients on fluvoxamine and in one ( 7 % ) on placebo . Statistically significant effects were seen on measures of social anxiety and general ( or anticipatory ) anxiety in patients treated with fluvoxamine compared with placebo . The level of phobic avoidance decreased also but the difference at endpoint between fluvoxamine and placebo failed to reach statistical significance . It is concluded that treatment with the SSRI fluvoxamine has beneficial effects in patients suffering from social phobia , suggesting that serotonergic mechanisms might be implicated in social anxiety CONTEXT The generalized type of social phobia ( social anxiety disorder ) is a severe and often disabling form of social anxiety that affects approximately 5 % of the general population . Earlier research has shown monoamine oxidase inhibitors or benzodiazepines to be effective in treating this condition , but neither has achieved widespread use . OBJECTIVE To compare the efficacy of paroxetine , a selective serotonin reuptake inhibitor , with placebo in adults with generalized social phobia . DESIGN Twelve-week , multicenter , r and omized , double-blind trial . SETTING Thirteen centers across the United States and 1 in Canada . PARTICIPANTS Between April 13 , 1995 , and February 28 , 1996 , 187 persons meeting Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria for generalized social phobia were r and omized ( and 183 returned for at least 1 efficacy assessment ) to treatment . INTERVENTION After a 1-week , single-blind , placebo , run-in period , patients received a double-blind , 11-week course of either paroxetine or matching-image placebo . The initial daily dosage of paroxetine ( or placebo ) was 20 mg with increases of 10 mg/d weekly ( flexible dosing to a maximum of 50 mg/d ) permitted after the second week of treatment . MAIN OUTCOME MEASURES Number of responders based on the Clinical Global Impression Global Improvement Item ( " much improved " or " very much improved " ) ; mean change from baseline on the Liebowitz Social Anxiety Scale total score . RESULTS Fifty ( 55.0 % ) of 91 persons taking paroxetine and 22 ( 23.9 % ) of 92 persons taking placebo were much improved or very much improved at the end of treatment ( odds ratio [ OR ] , 3.88 ; 95 % confidence interval [ CI ] , 2.81 - 5.36 ) . Mean Liebowitz Social Anxiety Scale total scores were reduced by 39.1 % ( the mean baseline score of 78.0 declined by a mean of 30.5 points at follow-up ) in the paroxetine group compared with 17.4 % ( the mean baseline score of 83.5 declined 14.5 points at follow-up ) in the placebo group , a difference of 21.7 % ( 95 % CI , 8.7%-34.7 % ) favoring paroxetine . CONCLUSIONS Paroxetine is an effective treatment for patients with generalized social phobia . Short-term ( ie , 11-week ) treatment results in substantial and clinical ly meaningful reductions in symptoms and disability . Future research should test whether these may be further reduced by extended treatment or supplementation with specific educational-cognitive-behavioral techniques Some evidence suggests that medications that modulate both serotonin and norepinephrine may be more effective than selective serotonin-reuptake inhibitors ( SSRIs ) in severe major depressive disorder ( MDD ) . This prospect i ve pragmatic trial tests this hypothesis . Patients with severe MDD were r and omly assigned to either duloxetine ( a serotonin and norepinephrine-reuptake inhibitor ) or physicians ’ choice of four generic SSRIs . Nonblinded , flexibly dosed treatment was used to mimic clinical practice . To address potential investigator bias , the patient-reported Quick Inventory of Depressive Symptomatology Self-Report ( QIDS-SR ) was used as the primary efficacy outcome measure . A total of 750 out patients ( 19.2 % , African descent ; 14.8 % , Hispanic ) were r and omized . The primary outcome , remission at week 12 by QIDS-SR , was numerically greater for duloxetine compared with SSRIs ( 36 vs. 32 % ) , but this difference was not statistically significant . Mean changes in secondary outcomes were significantly superior in favor of duloxetine for the Hamilton Depression Scale-17 item , the Brief Pain Inventory , and the Sheehan Disability Scale . Remission superiority on the QIDS-SR was not achieved . Significantly greater benefit for duloxetine compared with SSRIs was demonstrated on measures of pain and functioning . Study demographics suggest a more generalizable racial and ethnic population than is typical in r and omized clinical trials OBJECTIVE The purpose of this study was to determine the efficacy of fluvoxamine for the treatment of social phobia ( social anxiety disorder ) . METHOD In a 12-week multicenter , double-blind , r and omized , placebo-controlled trial , 92 patients with social phobia were treated with the selective serotonin reuptake inhibitor fluvoxamine ;  91.3 % of the patients had the generalized subtype of the disorder . The primary criterion for response was a rating of " much improved " or " very much improved " on the Clinical Global Impression of Improvement scale . Secondary response criteria were changes on three specialized rating scales for social phobia symptoms : the Brief Social Phobia Scale , the Social Phobia Inventory , and the Liebowitz Social Anxiety Scale . Psychosocial impairment was assessed in three domains ( disruption of work , social life , and home/family life ) by using the Sheehan Disability Scale . RESULTS The mean daily dose of fluvoxamine was 202 mg ( SD = 86 ) . At study end or with the last observation carried forward , within the evaluable subjects ( N = 86 ) there was a significantly higher proportion of responders in the fluvoxamine group ( 42.9 % , N = 18 ) than in the placebo group ( 22.7 % , N = 10 ) . Similarly , fluvoxamine was superior to placebo on all social phobia rating scales at week 8 and beyond . Fluvoxamine also result ed in significantly greater decreases in measures of psychosocial disability than did placebo . Overall , fluvoxamine was well tolerated and safe . CONCLUSIONS These findings indicate that fluvoxamine is efficacious in the pharmacologic management of serious forms of social phobia BACKGROUND Selective serotonin reuptake inhibitors ( SSRIs ) are the current gold st and ard in the pharmacologic treatment of generalized social phobia . SSRIs are only effective in approximately 50 % of individuals with generalized social phobia and can be associated with significant side effects . Based on the successful use of the anticonvulsants gabapentin and pregabalin in treating generalized social phobia , we conducted an open trial examining the efficacy of the glutamatergic and GABAergic anticonvulsant topiramate in the treatment of generalized social phobia . METHOD Twenty-three adult out patients with DSM-IV social phobia , generalized type , were entered into a 16-week open trial of topiramate , starting at 25 mg/day , and gradually titrated up to a maximum dose of 400 mg/day . RESULTS Twelve of 23 patients completed the trial . In the intent-to-treat ( ITT ) analysis , 11 ( 47.8 % ) of 23 were responders by a Clinical Global Impressions Improvement ( CGI-I ) scale rating of " much " or " very much " improved . The mean drop in the Liebowitz Social Anxiety Scale ( LSAS ) score for the ITT group was 29.4 % . The change in LSAS score from baseline to endpoint was significant for the ITT group ( F = 3.44 , df = 4,110 ; p = .01 ) . In the completers group , 9 ( 75.0 % ) of 12 were responders by CGI-I at 16 weeks , with a mean drop in LSAS score of 45.1 % . The rate of remission in the ITT sample , using a definition of an LSAS score of < /= 30 , gave a remission rate of 26.1 % ( 6/23 ) . CONCLUSION This study suggests that topiramate may be effective in the treatment of generalized social phobia . These results also suggest the possibility that the neurotransmitters glutamate and GABA may be involved in the neurobiology of generalized social phobia OBJECTIVE The authors evaluated the efficacy , safety , and tolerability of sertraline , a selective serotonin reuptake inhibitor , in the treatment of generalized social phobia . METHOD Adult out patients with generalized social phobia ( N=204 ) from 10 Canadian centers were r and omly assigned to receive sertraline or placebo in a 2:1 ratio for a 20-week double-blind study following a 1-week , single-blind , placebo run-in . The initial dose of sertraline was 50 mg/day with increases of 50 mg/day every 3 weeks permitted after the fourth week of treatment ( dosing was flexible up to a maximum of 200 mg/day ) . Primary efficacy assessment s were the percentage of patients rated much or very much improved on the Clinical Global Impression ( CGI ) improvement item and the mean changes from baseline to study endpoint in total score on the social phobia subscale of the Marks Fear Question naire and total score on the Brief Social Phobia Scale . RESULTS In intent-to-treat endpoint analyses of 203 of the patients , significantly more of the 134 patients given sertraline  ( N=71 [ 53 % ] ) than of the 69 patients receiving placebo  ( N=20 [ 29 % ] ) were considered responders according to their CGI improvement scores at the end of treatment . The mean reductions in the social phobia subscale of the Marks Fear Question naire and in the total score on the Brief Social Phobia Scale were 32.6 % and 34.3 % in the sertraline group and 10.8 % and 18.6 % in the placebo group , respectively . Analysis of covariance showed superiority of sertraline over placebo on all primary and secondary efficacy measures . Sertraline was well tolerated : 103 ( 76 % ) of the 135 sertraline-treated patients and 54 ( 78 % ) of the 69 placebo-treated patients completed the study . CONCLUSIONS Sertraline is an effective treatment for patients with generalized social phobia BACKGROUND Tricyclic antidepressants and selective serotonin reuptake inhibitors ( SSRIs ) as well as benzodiazepines have been shown to be effective for the treatment of panic disorder . The introduction of SSRIs has enabled a greater underst and ing of the role of serotonin in the etiology of panic disorder ; however , the role of norepinephrine has been more challenging to ascertain . The aim of this study was to determine the efficacy and tolerability of reboxetine , a novel selective norepinephrine reuptake inhibitor , in patients with panic disorder with and without agoraphobia . METHOD Eighty-two patients ( aged 18 - 65 years ) with DSM-III-R panic disorder , with or without agoraphobia , were r and omly assigned to receive 6 to 8 mg/day of reboxetine ( 42 patients ) or placebo ( 40 patients ) for 8 weeks in this placebo-controlled , parallel-group , double-blind clinical trial . RESULTS Of the 82 patients enrolled in the trial , 75 were considered in the analysis ( 37 patients in the reboxetine group and 38 patients in the placebo group ) . At last assessment , there was a significant reduction in the mean number of panic attacks ( range , 9.3 - 1.2 ) and phobic symptoms ( range , 8.1 - 3.2 ) in the reboxetine group compared with the placebo group ( ranges , 8.5 - 5.8 and 7.7 - 5.2 , respectively ; p < .05 ) . Improvement in Hamilton Rating Scale for Depression , Hopkins Symptom Checklist-90 , and Sheehan Disability Scale scores were also greater in the reboxetine group compared with the placebo group . Adverse events reported more frequently with reboxetine than placebo included dry mouth ( 36 % vs. 16 % ) , constipation ( 27 % vs. 22 % ) , and insomnia ( 26 % vs. 22 % ) . CONCLUSION Reboxetine was effective and well tolerated in the treatment of panic disorder The efficacy of irreversible and reversible monoamine oxidase inhibitors ( MAOIs ) in the treatment of social phobia ( SP ) is well established . Recently , selective serotonin reuptake inhibitors ( SSRIs ) have been used more frequently . In the present study , the efficacy and side-effect profile of citalopram , an SSRI , and moclobemide , the only MAOI used in Turkey , were compared . The 71 patients diagnosed with SP according to DSM-III-R were r and omly assigned to two subgroups ; citalopram ( n = 36 ) or moclobemide ( n = 35 ) . The study was an 8-week , r and omized , open-label , rater-blinded , parallel-group trial . All patients were assessed by Hamilton anxiety rating ( HAM-A ) , Liebowitz social anxiety ( LSAS ) , clinical global impression-severity of illness ( CGI-SI ) and clinical global impression-improvement ( CGI-I ) scales . There was a similar percentage of responders ( citalopram 75 % , n = 27 and moclobemide 74.3 % , n = 26 ) , with a > 50 % or greater reduction in LSAS total score and ratings of " very much " or " much improved " on the CGI-I. None of the patients withdrew from the study . The results of the present study suggest that citalopram has shown promising results in patients with SP Depressive disorders are a major health care issue and one of the foremost causes of disability in adults around the world , result ing in significant costs to society and health care systems ( 1 ) . The estimated economic burden associated with depression was $ 83.1 billion in 2000 and is probably higher today ( 2 ) . Depressive disorders include major depressive disorder ( MDD ) ; dysthymia ; and subsyndromal depression , including minor depression . Major depressive disorder is the most prevalent depressive disorder , with an estimated lifetime prevalence of 16 % in the United States ( 3 ) . An average of 8 million ambulatory care visits per year result in a primary diagnosis of MDD ( 4 ) . The American Psychiatric Association ( 5 ) defines MDD as depressed mood or loss of pleasure or interest along with other symptoms , including significant change in weight or appetite , insomnia or hypersomnia , psychomotor agitation or retardation nearly every day , fatigue or loss of energy , feelings of worthlessness or excessive or inappropriate guilt , indecisiveness or decreased ability to concentrate , and recurrent thoughts of death or suicide , that last for at least 2 weeks and affect normal functioning . Dysthymia is less severe , but symptoms last for 2 or more years . In contrast , subsyndromal depression is associated with less severe symptoms of depression that do not qualify for MDD or dysthymia diagnoses . The treatment of depression can be characterized by 3 phases ( Figure 1 ) : acute ( 6 to 12 weeks ) , continuation ( 4 to 9 months ) , and maintenance ( 1 year ) ( 7 ) . Relapse is defined as the return of depressive symptoms during the acute or continuation phases and is therefore considered part of the same depressive episode , whereas recurrence is defined as the return of depressive symptoms during the maintenance phase and is considered a new , distinct episode . Response to treatment ( typically defined as 50 % reduction in measured severity ) can be quantified using various tools , such as the Patient Health Question naire-9 ( PHQ-9 ) ( 7 ) or the Hamilton Depression Rating Scale ( HAM-D ) ( 8) . Figure 1 . Phases of treatment of major depression . Adapted from reference 6 . TX = treatment . Various treatment approaches can be used to manage MDD , such as psychotherapy , complementary and alternative medicine ( CAM ) , exercise , and pharmacotherapy . The psychological interventions used to treat depression include acceptance and commitment therapy , cognitive therapy , cognitive behavioral therapy ( CBT ) , interpersonal therapy , and psychodynamic therapies ( Table 1 ) . The CAM treatments include acupuncture , meditation , -3 fatty acids , S-adenosyl-l-methionine ( SAMe ) , St. John 's wort , and yoga . Exercise includes a broad range of activities that can be done for varying duration s , in classes , individually , or in informal groups . For pharmacologic therapy , the scope of this guideline is limited to second-generation antidepressants ( SGAs ) ( selective serotonin reuptake inhibitors , serotonin norepinephrine reuptake inhibitors , and selective serotonin norepinephrine reuptake inhibitors ) . First-generation antidepressants ( tricyclic antidepressants and monoamine oxidase inhibitors ) are very rarely used because SGAs have lower toxicity in overdose than first-generation antidepressants and similar efficacy . Table 1 . Common Psychological Interventions to Treat Depression Guideline Focus and Target Population The purpose of this guideline from the American College of Physicians ( ACP ) is to summarize and grade the evidence on the comparative effectiveness and safety of nonpharmacologic treatments and SGAs ( including serotonin reuptake inhibitors , serotonin norepinephrine reuptake inhibitors , bupropion , mirtazapine , nefazodone , and trazodone ) , alone or in combination , for MDD . The target audience for this guideline includes all clinicians , and the target patient population includes all adults with MDD . These recommendations are based on a background evidence article ( 9 ) and a systematic evidence review sponsored by the Agency for Healthcare Research and Quality ( AHRQ ) ( 6 ) . Methods Systematic Review of the Evidence The systematic evidence review was conducted by the AHRQ 's RTI InternationalUniversity of North Carolina at Chapel Hill Evidence -based Practice Center ( 6 ) . Additional method ological details can be found in the Appendix ) , accompanying background evidence article ( 9 ) , and full report ( 6 ) . Review ers search ed several data bases for studies published in English , German , or Italian from 1 January 1990 through September 2015 . Studies on efficacy were limited to r and omized , controlled trials and systematic review s and meta-analyses , although evidence on harms included observational studies . Review ers combined data when possible using meta- analysis and assessed the risk of bias and quality of studies according to established methods . The study population included adult out patients ( aged 18 years ) with MDD during either an initial or a second treatment attempt who did not remit after an initial adequate trial with an SGA . The review evaluated the following classes of interventions : depression-focused psychotherapy , CAM , exercise , and SGAs . Outcomes assessed included benefits in response ( often defined as 50 % improvement in HAM-D scores ) , remission ( often defined as a HAM-D score 7 ) , speed of response , speed of remission , relapse , quality of life , functional capacity ( as assessed by various scales ) , reduction of suicidality , or reduction of hospitalization . Harms assessed included overall adverse events , withdrawals because of adverse events , serious adverse events , and specific adverse events . Quality of life , functional status , suicidality , and hospitalizations were rarely reported . Grading the Evidence and Developing Recommendations This guideline was developed by the ACP Clinical Guidelines Committee according to the ACP guideline development process , which has been described ( 10 ) . The Clinical Guidelines Committee used the evidence tables in the accompanying systematic review and full report ( 9 ) when reporting the evidence and grade d the recommendations using ACP 's guideline grading system ( Table 2 ) . Table 2 . The American College of Physicians ' Guideline Grading System * Peer Review The AHRQ evidence review was sent to invited peer review ers and posted on the AHRQ Web site for public comments . The guideline was peer- review ed through the journal and was posted online for comments from ACP Governors and Regents . Comparative Benefits of Pharmacologic Versus Nonpharmacologic Treatment Options for Initial Management Refer to Appendix Table 1 and the accompanying systematic review ( 9 ) for additional details of the evidence . Appendix Table 1 . First-Line Treatment for MDD : SGAs Versus Nonpharmacologic Therapies * SGA Versus Psychological Interventions SGA Versus CBT Monotherapy . Moderate- quality evidence from 5 trials ( 1115 ) showed no difference in response when comparing SGAs ( fluoxetine , fluvoxamine , paroxetine , or sertraline ) with CBT in patients with MDD after 8 to 52 weeks of treatment . Low- quality evidence from 3 trials ( 11 , 14 , 15 ) showed no difference between remission rates ( fluoxetine , fluvoxamine , and paroxetine ) and functional capacity ( 14 ) ( fluvoxamine and paroxetine ) for SGAs compared with CBT . Combination Therapy . Low- quality evidence from 2 trials ( 14 , 16 ) showed no difference in response or remission when comparing monotherapy using SGAs ( escitalopram , fluvoxamine , or paroxetine ) with combination therapy using SGAs plus CBT ( problem-solving therapy or telephone-based CBT ) in patients with MDD after 12 to 52 weeks of treatment . Low- quality evidence from 2 trials ( 14 , 16 ) assessed function , and 1 trial showed that patients who received the combination therapy reported more improvement on 3 of 5 work-functioning measures than those who received SGA monotherapy , although clinical ly important differences on these measures are uncertain . SGA Versus Interpersonal Therapy Monotherapy . Low- quality evidence showed no difference in response ( 1 trial ; escitalopram ) ( 17 ) or remission ( 2 trials ; citalopram , escitalopram , or sertraline ) ( 17 , 18 ) for SGAs compared with interpersonal therapy for patients with MDD after 12 weeks of treatment . Combination Therapy . Low- quality evidence from 1 trial ( 19 ) showed increased remission for SGA monotherapy compared with SGA combined with interpersonal therapy ( with nefazodone ) in patients with MDD after 12 weeks of treatment . SGA Versus Psychodynamic Therapies Monotherapy . Low- quality evidence from 1 trial ( 20 ) showed no difference in remission for fluoxetine compared with psychodynamic monotherapy in patients with MDD after 16 weeks of treatment . Low- quality evidence from 2 trials ( 20 , 21 ) showed few differences in functional capacity between the treatments . Combination Therapy . Low- quality evidence from 1 trial ( 21 ) showed no difference in functional capacity for SGA monotherapy compared with SGA plus psychodynamic combination therapy . SGA Versus CAM Interventions SGA Versus Acupuncture Monotherapy . Low- quality evidence from 2 trials ( 22 , 23 ) showed no difference in treatment response when comparing fluoxetine with acupuncture monotherapy for patients with MDD after 6 weeks of treatment . Combination Therapy . Low- quality evidence from 2 trials ( 24 , 25 ) showed that combination therapy of SGAs with acupuncture improved treatment response compared with monotherapy with SGAs ( fluoxetine or paroxetine ) in patients with MDD after 6 weeks of treatment . However , low- quality evidence from 1 trial ( 24 ) showed no difference in remission when comparing paroxetine monotherapy with paroxetine plus acupuncture combination therapy . SGA Versus -3 Fatty Acids Monotherapy . Low- quality evidence from network meta- analysis showed that SGAs ( fluoxetine ) were associated with a greater response than -3 fatty acids in patients with MDD .  SGA Versus SAMe Monotherapy . Low- quality evidence from network meta- analysis showed no difference in response between treatment with escitalopram OBJECTIVES New treatment options for dementia and its behavioral disturbances have become available since publication of The Expert Consensus Guidelines on the Treatment of Agitation in Older Persons with Dementia in 1998 . While only 2 cholinesterase inhibitors , donepezil and tacrine , were available in 1998 , 3 new cognitive-enhancing agents have been introduced since that time as well as several new atypical antipsychotics and antidepressants . However , there are still limited data from controlled studies to guide clinicians in choosing among these agents and sequencing and combining treatments . We therefore conducted a new survey study of expert opinion on the treatment of cognitive impairment and behavioral disturbances associated with dementia . METHODS Based on a literature review , a 61- question survey was developed with 1,225 options . Most options were scored using a modified version of the R AND 9-point scale for rating appropriateness of medical decisions . For other options , the experts were asked to write in answers . The survey was sent to 50 North American experts on dementia , 100 % of whom completed it . In analyzing responses to items rated on the 9-point scale , consensus was defined as a nonr and om distribution of scores by chi-square " goodness-of-fit " test . Based on the 95 % confidence interval around the mean , we assigned a categorical rank ( first line/preferred , second line/alternate , third line/usually inappropriate ) to each option . Guidelines indicating preferred treatment strategies were then developed for selected clinical situations . RESULTS For patients at risk for dementia , the experts recommended control of hypertension and diabetes . They also recommended aspirin and would consider a lipid-lowering agent in patients at risk for vascular dementia . Cholinesterase inhibitors were an option for patients with mild cognitive impairment ( i.e. , at risk for Alzheimer 's dementia [ AD ] ) . To slow cognitive impairment in mild/moderate AD , the experts recommended a cholinesterase inhibitor alone or combined with vitamin E. Donepezil and  galantamine  were the preferred cholinesterase inhibitors . The experts recommended combining a cholinesterase inhibitor with a N-methyl-D-aspartate ( NMDA ) antagonist ( e.g. , memantine ) if a patient with mild/moderate dementia has an inadequate response to monotherapy . Control of hypertension and diabetes was the treatment of choice , in patients with mild/moderate vascular or mixed AD/vascular dementia , with aspirin another first-line option . Cholinesterase inhibitors were also a first-line option for mild/moderate mixed AD/vascular dementia . Among nonpharmacological interventions for mild/moderate dementia , the experts recommended caregiver education , supportive therapy for caregivers , referral to day treatment , exercise programs , and respite care . For moderate/severe AD or mixed AD/vascular dementia , the experts recommended combining an NMDA antagonist with a cholinesterase inhibitor . For moderate/severe vascular or mixed AD/vascular dementia , they recommended control of hypertension and diabetes . The experts ' ratings underscore the importance of nonpharmacological strategies aim ed at reducing caregiver burden in more severe dementia . Management of agitation and other behavioral disturbances was another focus of this study . The experts recommended using an atypical antipsychotic for agitation associated with delirium , psychosis , aggression , or anger . They would also consider divalproex to manage anger with a risk of physical aggression . Selective serotonin reuptake inhibitors were recommended for the treatment of depression or anxiety in patients with dementia . Benzodiazepines or atypical antipsychotics were viewed as short-term options for acute anxiety .  Trazodone was recommended for insomnia . The experts also gave recommendations concerning dosage levels , duration of treatment , and choice of medications for patients with different complicating conditions . CONCLUSIONS The experts reached high levels of consensus on key steps in treating dementia and associated behavioral disturbances . Within the limits of expert opinion and with the expectation that new research data will take precedence , these guidelines may provide direction for clinicians offering care to patients with dementia Objective : To review the mechanism of selective serotonin reuptake inhibitor (SSRI)–mediated serotonergic neurotransmission , focusing on serotonin 1A ( 5-HT1A ) autoreceptors , which are proposed to be involved in delaying therapeutic efficacy . Vilazodone was specifically design ed to function both as an SSRI and a partial agonist at 5-HT1A receptors . This combined mechanism is proposed to decrease time to efficacy , minimize sexual side effects , and provide concomitant anxiolytic properties . Data Sources : A PubMed search of all English- language articles from January 1990 to January 2013 was conducted using the search terms depression and 5-HT1A , depression and buspirone , depression and pindolol , and vilazodone . Study Selection : We found 47 articles and abstract s that were selected for inclusion on the basis of information about the pharmacology of 5-HT1A receptors and the clinical data on pindolol , buspirone , and vilazodone in depression . Data Extraction : This review summarizes current literature involving antidepressant activity , the role of 5-HT1A autoreceptors , and clinical trials involving serotonin reuptake inhibition in conjunction with 5-HT1A agonists and partial agonists , with a focus on vilazodone . Results : Vilazodone has demonstrated efficacy in 2 large , r and omized , double-blind , placebo-controlled trials in major depressive disorder . Results suggest that vilazodone has a low incidence of sexual side effects and is effective in patients with high levels of anxiety . A pooled analysis shows evidence of significant symptom reduction after only 1 week of therapy . Conclusions : If future studies corroborate the clinical benefits attributed to its mechanism of action , vilazodone may show potential advantages in terms of onset of action , sexual side effects , and anxiolytic activity in patients with major depressive disorder The objective of the study was to examine the efficacy of fluoxetine in  social phobia . Sixty subjects were r and omly assigned to 14 weeks of double-blind therapy with either fluoxetine or placebo . Dose was fixed at 20 mg for fluoxetine during the first 8 weeks of double-blind treatment ; during the final 6 weeks , the dose could be increased every two weeks by 20 mg to a maximum of 60 mg/day . An intentto-treat analysis was used . A significant change from baseline to endpoint was found for both fluoxetine and placebo on the Liebowitz Social Anxiety Scale . However , no significant difference was found between fluoxetine and placebo . The change for fluoxetine was somewhat lower than that found with other selective serotonin reuptake inhibitors , whereas the placebo response was greater .  Fluoxetine failed to separate from placebo in this trial . It is unknown whether a larger dose for longer duration would have yielded separation from placebo . A higher than usual  placebo response rate was found Abstract Objective . Anxiety disorders are frequently under-diagnosed conditions in primary care , although they can be managed effectively by general practitioners . Methods . This paper is a short and practical summary of the World Federation of Biological Psychiatry ( WFSBP ) guidelines for the pharmacological treatment of anxiety disorders , obsessive – compulsive disorder ( OCD ) and posttraumatic stress disorder ( PTSD ) for the treatment in primary care . The recommendations were developed by a task force of 30 international experts in the field and are based on r and omized controlled studies . Results . First-line pharmacological treatments for these disorders are  selective serotonin reuptake inhibitors  ( for all disorders ) ,  serotonin-norepinephrine reuptake inhibitors  ( for some ) and  pregabalin  ( for generalized anxiety disorder only ) . A combination of  medication and cognitive behavior/exposure therapy  was shown to be a clinical ly desired treatment strategy . Conclusions . This short version of an evidence -based guideline may improve treatment of anxiety disorders , OCD , and PTSD in primary care The augmentation of serotonin reuptake inhibitors ( SRIs ) with atypical antipsychotics for the management of  treatment-resistant obsessive-compulsive disorder ( OCD ) is gaining increasing acceptance . Quetiapine is a novel antipsychotic which is well tolerated , and which may therefore be particularly useful in this context . Charts of all patients treated in our OCD clinic with the combination of an SRI and quetiapine  were review ed . Demographic details and clinical symptoms on the Yale-Brown Obsessive-Compulsive Scale and the Clinical Global Impressions Scale ( CGI ) were tabulated before and after augmentation . Eight OCD patients who had proven resistance to treatment with SRIs  had received quetiapine augmentation . Four of these eight patients were responders ( CGI of 1 or 2 ) within 4 weeks . In the treatment-responders , the medication was well tolerated . Although limited by the retrospective design and lack of controls , these data are consistent with the growing literature suggesting that approximately one-half of OCD patients resistant to treatment with SRIs  may respond to augmentation with an atypical antipsychotic . Quetiapine , a relatively well tolerated agent , deserves further controlled study in this context Abstract : Venlafaxine extended release ( ER ) is a dual serotonin-norepinephrine reuptake inhibitor previously shown to be effective in the treatment of major depressive disorder and generalized anxiety disorder . This placebo-controlled , multicenter , r and omized , double-blind trial examined the efficacy and safety of venlafaxine ER in out patients with generalized social anxiety disorder . Two hundred seventy-two out patients were r and omly assigned to receive either a flexible dose of venlafaxine ER ( 75 to 225 mg/d ) or placebo for 12 weeks . Venlafaxine ER was statistically significantly more effective than placebo as demonstrated by the Liebowitz Social Anxiety Scale total scores at weeks 4 to 12 . Scores of both the Clinical Global Impression-Severity and Clinical Global Impression-Improvement scales showed that venlafaxine ER was significantly more effective than placebo at weeks 4 to 12 . In addition , more venlafaxine ER-treated patients achieved CGI-Improvement scores of 1 or 2 than placebo-treated patients at weeks 4 to 12 , demonstrating a greater percentage of responders to venlafaxine ER treatment . Assessment using the fear/anxiety and avoidance subscales of the Liebowitz Social Anxiety Scale and the Social Phobia Inventory Scale also showed venlafaxine ER to be more effective than placebo at weeks 4 to 12 and 6 to 12 , respectively . The Sheehan Disability Inventory showed that patients in the venlafaxine ER-treated group had significantly better outcomes in social life at weeks 4 and 12 , and in work at week 12 . Adverse events were similar to those reported in studies of venlafaxine ER in depression and generalized anxiety disorder .  Venlafaxine ER was safe , well tolerated , and efficacious in the short-term treatment of generalized social anxiety disorder OBJECTIVE Recently , pharmacological treatment guidelines for panic disorder have changed as newer treatment options have become available . The authors examined how the use of psychotropic drugs has shifted over the course of 10 years to determine if prescribing patterns have changed to reflect these revised treatment guidelines . METHOD A total of 443 patients with panic disorder were enrolled in the Harvard/Brown Anxiety Research Project , a prospect i ve longitudinal study of anxiety disorders . These patients were interviewed over the course of 10 years to examine their use of psychotropic medications . RESULTS Despite efforts aim ed at increasing the use of selective serotonin reuptake inhibitors ( SSRIs ) in patients with panic disorder ( e.g. , APA 's practice guideline for panic disorder , Food and Drug Administration approval of particular SSRIs for the treatment of panic disorder ) , only a modest increase in their use was found . Treatment patterns for psychotropic drugs  appear to have remained stable over the past decade , with benzodiazepines being the most commonly used medication for panic disorder . In comparison , SSRI use throughout the follow-up period has remained low . Patients using an SSRI did not have a more favorable clinical course than those using a benzodiazepine , nor were there significantly better rates of remission in patients using SSRIs and benzodiazepines concomitantly . CONCLUSIONS These results highlight a gap between pharmacological treatment guidelines and actual delivery of care in that recommendations to use SSRIs to treat panic disorder are not being followed . Factors potentially associated with promoting and ignoring treatment recommendations are discussed Introduction Pharmacotherapy and cognitive behavioural therapy ( CBT ) are consistently effective as first-line treatments for  social anxiety disorders ( SADs ) . Nevertheless , pharmacotherapy is often the first choice in clinical practice . In many countries , the first line of pharmacotherapy involves the administration of a selective serotonin reuptake inhibitor ( SSRI ) . Although a significant proportion of patients with SAD fail to respond to the initial SSRI administration , there is no st and ard approach to the management of SSRI-resistant SAD . This paper describes the study protocol for a r and omised controlled trial to evaluate the clinical effectiveness of CBT as a next-step strategy , concomitant with conventional treatment , for patients with SSRI-resistant SAD . Methods and analysis This Prospect i ve R and omized Open Blinded End-point study is design ed with two parallel groups , with dynamic allocation at the individual level . The interventions for the two groups are conventional treatment , alone , and CBT combined with conventional treatment , for 16 weeks . The primary end-point of SAD severity will be assessed by an independent assessor using the Liebowitz Social Anxiety Scale , and secondary end-points include severity of other social anxieties , depressive severity and functional impairment . All measures will be assessed at weeks 0 ( baseline ) , 8 ( halfway point ) and 16 ( postintervention ) and the outcomes will be analysed based on the intent-to-treat . Statistical analyses are planned for the study design stage so that field material s can be appropriately design ed . Ethics and dissemination This study will be conducted at the academic outpatient clinic of Chiba University Hospital . Ethics approval was granted by the Institutional Review Board of Chiba University Hospital . All participants will be required to provide written informed consent . The trial will be implemented and reported in accordance with the recommendations of CONSORT . Clinical Trial Registration Number UMIN000007552
Cognitive behavior therapy  appears to be more effective than other evidence -based psychological techniques , and its effects appear to be more enduring than those of pharmacotherapy .
There is some evidence , albeit limited to certain drug classes , that the combination of  medication and cognitive behavior therapy may be more effective than either strategy used alone .
This article proposes a number of recommendations for the treatment of  generalized social phobia  , based on a systematic literature review and meta- analysis .
For medications , selective serotonin reuptake inhibitors and dual serotonin-norepinephrine reuptake inhibitors are first-line choices based on their efficacy and tolerability profiles .
There are other medication classes with demonstrated efficacy in social phobia ( benzodiazepines , antipsychotics , alpha-2-delta lig and s ) , but due to limited published clinical trial data and the potential for dependence and withdrawal issues with benzodiazepines , it is unclear how best to incorporate these drugs into treatment regimens .