Clinical trial NCT06001021
Conditions: Perinatal Depression Perinatal Anxiety
Keywords: Cognitive Behavioral Couple Therapy (with or without Zikr) Pharmacology Intervention Their combination
Sponsor: Sameera Shafiq
Start date: 2023-08-15; Completion date: 2023-10-28
Enrollment: 96 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The hypotheses of the study are

* There will be differences in perceived perinatal distress, dyadic coping strategies, social support, domains of quality of life, and well-being in couples at Pre- and Post-Test levels during the perinatal period in couples.
* There will be differences with psychopharmacological intervention on total scores of perceived perinatal distress, dyadic coping strategies, social support, domains of quality of life, and well-being between the experimental and wait list-placebo control groups.
* There will be differences in CBCT (condition: without Zikr) on total scores of perceived perinatal distress, dyadic coping strategies, social support, domains of quality of life, and well-being between the experimental and wait list control group.
* There will be differences in CBCT (condition: with Zikr) on total scores of perceived perinatal distress, dyadic coping strategies, social support, domains of quality of life, and well-being between the experimental and wait list-placebo control groups.
* There will be differences for combined psychopharmacology, and CBT (conditions: with Zikr, without Zikr ) dimensions on total scores of perceived perinatal distress, dyadic coping strategies, social support, domains of quality of life, and well-being between experimental and wait list-placebo control group.

Detailed description:
The research questions of the study are

• How effective will psychopharmacological treatment, CBCT (with or without Zikr) and combined medicine-CBCT (with or without Zikr) interventions be in reducing symptoms of distress among couples during the perinatal period through a randomized clinical trial?

* Will dyadic coping strategies, social support, domains of quality of life, and well-being be improved in couples at the post-test level compared to the pre-test level by therapeutic intervention through a randomized clinical trial?
* What will be the effect size of post-test intervention?

Procedures and Protocol

The investigator will ask willing participants (screened for high risk) to select one of their preferred treatment modes out of the following

1. Medications (antidepressants and/or anxiolytics).
2. Cognitive Behavioural Therapy without Zikr.
3. Cognitive Behavioural Therapy with Zikr.
4. Combination of medications and cognitive behavioral therapy.
5. Combination of medications, cognitive behavioral therapy, and Zikr.

   A list of willing participants will be prepared. Each participant will have one in five chances of getting the preferred treatment mode after study is over. There will be two groups (experimental and control). To put people into one of the two groups, the investigator will select by randomization via online calculator random number generation.

   Participants will not know to which group they actually belong. This information will be recorded in the investigator's files, but the research assistant will not look at these files until after the research is finished. This is the best way the investigators have to testing without being influenced by what they think or hope might happen. Thus, the participants and the research assistant will be double blinded in the trial. The investigator and research assistant will then compare which of the two has the best results.

   The healthcare professionals (consultant gynecologists and investigator's research assistant) will be looking after the participants very carefully during the study. If there are anything participants are concerned about or that is bothering them about the research they will talk to the researcher, research assistant, gynaecologist or staff.

   A placebo or inactive medicine looks like real medicine but it is not. It is a dummy or pretend medicine. It has no effect on a person because it has no real medicine in it. The investigator wants to know whether medicine is good, therefore some people will be given the medicine and others will be given the pretend or a dummy medicine. For the research to be good, it is important that participants do not know whether they have been given real medicine or pretend or dummy medicine. This is one of the best ways the investigator have for knowing what the medicine that are being tested really does. But the participants given a placebo or no intervention will be informed at the end of the study and will be given treatment with medication as they are wait-list control. Moreover, the participants in the intervention group will receive their preferred treatment after the completion of the study.

   Participants will receive psychopharmacological treatment according to the National Institute for Health and Care Excellence (NICE) guidelines.

   Description of the Process

   During the research, a couple has to make ten visits to attend ten sessions in the hospital.

   • In the first visit, rapport will be built and pre-test assessment will be done in the following two approaches

   Quantitative Approach

   • Indigenously developed Parental Perinatal Distress Scale (PPDS).
   * Multidimensional Scale for Perceived Social Support (MSPSS).
   * Dyadic Coping Inventory (DCI).
   * Flourishing Scale (FS).
   * World Health Organization's Quality of Life Brief (WOLQOL-BREF)

   Qualitative Approach • In a qualitative approach, the semi-structured interviews will be conducted to explore the present stressors and expectations, and perceptions about the effectivity of treatments for perinatal distress among couples.

   Group 1 will be given medications or placebo for two weeks and/or for four to five weeks maximum (as per requirement) by the consultant gynaecologist. They have to visit after two weeks for post-test assessment. After treatment, the medicine will be tapered off to stop the intake. As explained before, neither participant will know whether they have received the medicine or the placebo. But in the end placebo participants will be debriefed and will be continued with real medication.

   Group 2, Group 3, Group 4 and Group 5 will continue the following 10 sessions (two sessions, each one hour per week) of CBCT with the investigator.

   • In the second session, participants will be psycho-educated for perinatal period distress, couples' physical and mental health and impact on the fetus-infant, the prevalence of depression and anxiety, and the significance of identification. Progressive muscle relaxation exercises will be carried out along with deep breathing. Feedback on the session will be taken.

   • In the third session, participants will be psycho-educated on the theoretical model of cognitive-behavioral couple therapy with some historical highlights and empirical standing. A thought log will be given for homework. Feedback for deep breathing and progressive muscle relaxation will be carried out.

   • In the fourth, fifth, sixth, seventh, eighth, and ninth session, feedback will be taken on homework and session. Various techniques of Cognitive Behavioural Couple Therapy will be applied based on the nature and contents of identified precipitating, perpetuating, and present stressors. In addition, relevant techniques will be incorporated from other modalities with eclecticism. Tasbeeh in Zikr will be given to group 3 and group 5 who opted for it in the screening process.

   • On the tenth visit, feedback on the session and homework will be taken. post-test assessment will be done in the following two approaches Group 6 will be exposed to one of the two conditions. 50% of couples will get a placebo and 50% will receive routine treatment care with no intervention. However, after the completion of the research, intervention groups and waitlist group (control) will be briefed and will be delivered with an intervention mode of treatment of their choice as selected earlier.

   Posttest assessment will be carried out by the following instruments Quantitative Approach • Indigenously developed Parental Perinatal Distress Scale (PPDS). • Multidimensional Scale for Perceived Social Support (MSPSS). • Dyadic Coping Inventory (DCI).

   • Flourishing Scale (FS).
   * World Health Organization's Quality of Life Brief (WOLQOL-BREF) Qualitative Approach
   * In a qualitative approach, the semi-structured interview will be conducted to explore the conception about the perinatal distress and perceptions about effectivity of treatments for perinatal distress among couples.

   Duration The research takes place from 15th August, 2023 to 30th September, 2023. Screening (for Major Depressive Disorder, Generalized Anxiety Disorder) with PPDS will be carried out on the couples who visit the gynecological ward of the hospital in August. After screening and signed informed consent, it will be necessary for participants to come to the clinic/hospital for 10 days in total, for one hour session each day in end of August and whole month of September (two sessions per week, each for one hour).

   The investigator and the research assistant would like to meet with participants twice in the upcoming month after the participant's last session visit for a final check-up in follow-ups.

Arms: arm 1: This group will receive psychopharmacological intervention with perinatal safe light doses of antidepressants (see Langan et al., 2016; Schoretsanitis et al., 2021) and/or anxiolytic medications (see Nishimura et al, 2021; Saito et al, 2022) by a gynecologist. Selective Serotonin Reuptake Inhibitor (Escitalopram, 5-10 mg in pregnancy and Sertraline, 12.5-25 mg in postpartum) and/or Benzodiazepine (Alprazolam, 0.25-0.5 mg) will be prescribed in tablet form per day. arm 2: This group will receive CBCT intervention from a trained psychologist in CBT. There are two conditions of CBCT, i) with Zikr, and ii) without Zikr. arm 3: This group will receive Medicine (prescribed by a consultant gynecologist) and CBCT intervention (with or without Zikr) from a trained psychologist in CBT. arm 4: This group will receive a placebo from a gynecologist or no intervention from a trained psychologist. arm 5: This group will receive no intervention from a trained psychologist.
Interventions: intervention 1: Psychopharmacological Intervention intervention 2: Cognitive Behavioral Couple Therapy intervention 3: Combination of Psychopharmacological Intervention and CBCT intervention 4: Placebo and No Intervention
Intervention descriptions: intervention 1: Escitalopram 5-10 mg in antenatal period; Sertraline 12.5-25 mg in postnatal period) and/or Benzodiazepine (Alprazolam, 0.25-0.50 mg). intervention 2: CBCT intervention from a trained psychologist in CBT. intervention 3: Medication will be prescribed by a consultant gynecologist and CBCT (conditions: with or without Zikr) will be provided by a trained psychologist. intervention 4: Control waitlist group will be provided with either a placebo by a consultant gynaecologist or no intervention by a trained psychologist

Protocol documents:
ICF_002.pdf: 
 
 
 
                               Informed Consent Form  
                                      Health Care Professional (Consultant Gynaecologist) 
 
Research Project: "The Effectiveness of Psychopharmacological Intervention versus Cognitive Behavioural 
Couple Therapy and Their Combination in Perinatal Distressed Couples: A Randomized Clinical Trial"  
Principal Investigator: Ms Sameera Shafiq (Ph.D. Scholar and Lecturer) 
Department of Psychology, University of Gujrat, Gujrat, Pakistan. 
 
Unique Protocol ID: UOG/ORIC/2022/393  
Brief Title: Cognitive Behavioral Couple Therapy for Perinatal Distress  
Registration: NCT06001021 
Initial Registration: 26th June, 2023. 
Initial Approval and Public Release Date: 13th August, 2023. 
Sponsor/Funder: Nil 
 
The informed consent form consists of two parts:  
• 
Information Sheet (to share information about the research with you) 
• 
Certificate of Consent (for signatures if you agree to take part) 
PART I: Information Sheet 
Introduction 
I am Ms. Sameera Shafiq/Mrs Sameera Ahmed conducting a research study on couple’s perinatal distress. I 
am going to give you information and invite you to be part of this research as a health care professional.  
Purpose of the Research 
Perinatal Distress (such as depression and/or anxiety) is a growing concern nowadays and is observed in 
couples (wives and husbands) during antenatal and postnatal period. It might effect the family and the 
foetus-infant badly if left unnoticed. NICE guidelines have recommended screening and treating perinatal 
women for depression and anxiety (see Annexure A).  Researches showed that perinatal distress can be 
treated with psychotropic medications, cognitive behavioural therapy and/or a combination of both. The 
reason we are doing this research is to find out if the medications (antidepressant and/or anxiolytics) are 
better than cognitive behavioural therapy or combination of both as a treatment for perinatal distress in the 
couples.   
Type of Research Intervention 
This research study involves the following treatments 
1) Medications (antidepressants and/or anxiolytics). 
2) Cognitive Behavioural Therapy without Zikr. 
3) Cognitive Behavioural Therapy with Zikr. 
4) Combination of medications and cognitive behavioural therapy. 
5) Combination of medications, cognitive behavioural therapy, and zikr. 


Participant Selection 
We will inviting all women (4th month to 7th month in antenatal period; after a week till one year of a child in 
postnatal period) and selecting willing couples with perinatal distress (high-risk) who attends gynaecology of 
the hospital to participate in the research with the treatment offered for free. The age range will be between 
19 to 45 years.  
Voluntary Participation 
Participation in this research is entirely voluntary. It is participant’s’ choice whether to participate or not. If 
participants choose not to participate in this research project, they will offer the treatment that is routinely 
offered in this clinic/hospital. Participants may change your mind later and stop participating even if you 
agreed earlier. 
Information on the Trial Medicine [Antidepressants and anxiolytics] 
1) The antidepressants and/or anxiolytics safe in antenatal (2nd and 3rd trimester) and postnatal period will be 
prescribed.  
2) Anxiolytics used to control symptoms of anxiety without serious impairment of normal physical or mental 
function. Antidepressants reduce mood swings and improve overall wellbeing. 
3) Some common side effects of antidepressants include feeling agitated, shaky, indigestion and stomach 
aches, diarrhoea or constipation, loss of appetite, dizziness, not sleeping well, or feeling very sleepy, 
headaches. Some short-term side effects of anxiolytics can include Low heart rate, Low blood pressure, Irregular 
breathing, Confusion, Dizziness, Nausea. These side effects are temporary and will be settled down in two weeks 
and the medication will start working for normalization of mood and/or reduction of anxiety.  
Procedures and Protocol 
We will ask willing participants (screened for high risk) to select one of their preferred treatment modes out 
of the following 
1) Medications (antidepressants and/or anxiolytics). 
2) Cognitive Behavioural Therapy without Zikr. 
3) Cognitive Behavioural Therapy with Zikr. 
4) Combination of medications and cognitive behavioural therapy. 
5) Combination of medications, cognitive behavioural therapy, and Zikr. 
A list of willing participants will be prepared. Each participant will have one in five chances of getting the 
preferred treatment mode. There will be two groups (experimental and control). To put people into one of 
the two groups, we will select by chance as for instance by random number generated by a research assistant.  
Participants will not know to which group they actually belong. This information will be in our files, but we 
will not look at these files until after the research is finished. This is the best way we have for testing without 
being influenced by what we think or hope might happen. We will then compare which of the two has the 
best results. If there are anything participants are concerned about or that is bothering them about the 
research they will talk to the researcher, research assistant, gynaecologist or staff.  
A placebo or inactive medicine looks like real medicine but it is not. It is a dummy or pretend medicine. It 
has no effect on a person because it has no real medicine in it. We want to know whether medicine is good, 
we give some people the medicine and some people the pretend or dummy medicine. For the research to be 
good, it is important that participants do not know whether they have been given the real medicine or the 
pretend or dummy medicine.  This is one of the best ways we have for knowing what the medicine we are 
testing really does. But the participants given placebo will be informed in the end of the study and will be 
given treatment with medication.  
Description of the Process 
During the research a couple has to make ten visits to attend ten sessions in the hospital. 


 In the first visit, rapport will be build and pre-test assessment will be done in the following two 
approaches 
Quantitative Approach 
 Indigenously developed Parental Perinatal Distress Scale (PPDS). 
 Urdu version (Akhtar, Rahman, Husain, Chaudhry, Duddu,… & Husain, 2010) of Multidimensional 
Social Support Scale (Zimet, Dahlem, Zimet, & Farley, 1988).  
 Urdu version (Shujja, Adil, Randall, Bodenmann, & Malik, 2020) of Dyadic Coping Inventory 
(Bodenmann, 2008).  
 Urdu version (Choudhry, Al-Worafi, Akram, Ahmed, Anwar ul Haq, Khan,…  & Golden, 2018) of 
Flourishing Scale (Diener, Wirtz, Tov, Kim-Prieto, Choi, Oishi, & Biswas-Diener, 2009).  
 Urdu version (Lodhi, Raza, Montazeri, Nedjat, Yaseri, & Holakouie-Naieni, 2017) of World Health 
Organization’s Quality of Life Brief (WHOQOL Group, 1998).  
Qualitative Approach 
 Semi-structured interview will be conducted to explore the present stressors and expectations and 
perceptions about effectivity of treatments for perinatal distress among couples.  
Group 1 will be given medications or placebo for two weeks and/or for four to five weeks maximum. They 
have to visit after two weeks for post-test assessment. As explained before, neither participant will know 
whether they have received the medicine or the placebo. But in the end placebo participants will be 
debriefed and will be continued with real medication. Consultant gynaecologist will prescribe medication 
after thorough risk-benefit evaluation.  
Group 2, Group 3, and Group 4 will continue the following sessions 
 In the second session, participants will be psycho-educated for perinatal period distress, couples’ 
physical and mental health and impact on the foetus-infant, prevalence of depression and anxiety and 
significance of identification. Progressive muscle relaxation exercise will be carried out along with 
deep breathing. Feedback on the session will be taken. 
 In the third session, participants will be psycho-educated for the theoretical model of cognitive 
behavioural couple therapy with some historical highlights and empirical standing. Thought log will 
be given for homework. Feedback for deep breathing and progressive muscle relaxation will be 
carried out.  
 In the fourth, fifth, sixth, seventh, eighth and ninth session, feedback will be taken on homework and 
session. Various techniques of Cognitive Behavioural Couple Therapy will be applied based on the 
nature and contents of identified precipitating, perpetuating, and present stressors. In addition, 
relevant techniques will be incorporated from other modalities with eclecticism. Tasbeeh (see Shafiq 
et al., 2022) in Zikr will be given to group 3 and group 5 who opted for it in screening process.  
 In the tenth visit, feedback on session and homework will be taken. post-test assessment will be done 
in the following two approaches 
Group 5 will be exposed to one of the two conditions. 50% couples will get placebo and 50% will receive 
the routine treatment care with no intervention. However, after the completion of the research, this waitlist 
group (control) will be briefed and will be delivered with intervention mode of treatment.  
Quantitative Approach 
 Indigenously developed Parental Perinatal Distress Scale (PPDS) 
 Urdu version (Akhtar, Rahman, Husain, Chaudhry, Duddu, & Husain, 2010) of Multidimensional 
Social Support Scale (Zimet, Dahlem, Zimet, & Farley, 1988).  
 Urdu version (Shujja, Adil, Randall, Bodenmann, & Malik, 2020) of Dyadic Coping Inventory 
(Bodenmann, 2008).  
 Urdu version (Choudhry, Al-Worafi, Akram, Ahmed, Anwar ul Haq, Khan, … & Golden, 2018) of 
Flourishing Scale (Diener, Wirtz, Tov, Kim-Prieto, Choi, Oishi, & Biswas-Diener, 2009).  


 Urdu version (Lodhi, Raza, Montazeri, Nedjat, Yaseri, & Holakouie-Naieni, 2017) of World Health 
Organization’s Quality of Life Brief (WHOQOL Group, 1998).  
Qualitative Approach 
 Semi-structured interview will be conducted to explore the present stressors and expectations and 
perceptions about effectivity of treatments for perinatal distress among couples.  
Duration  
The research takes place over from 15th August, 2023 to 30th October, 2023. Screening with PPDS will be 
carried out on the couples who visit gynaecological ward of the hospital in July. After screening, enrolment, 
and signed informed consent, it will be necessary for participants to come to the clinic/hospital for 10 days in 
total, for one hour session each day in last week of August (two days per week, each for one hour) till 
September. A follow-up visit after two weeks in October is compulsory. In a follow-up qualitative approach 
of interviewing will be used.  
Reimbursements 
We will give participants [PKR. 500/-] to pay for their travel to the clinic. Participants will not be given any 
other money or gifts to take part in this research. 
Confidentiality 
The information that we collect from this research project will be kept confidential. Information about 
participants that will be collected during the research will be put away and no-one but the researchers will be 
able to see it. Any information about participants will have a number on it instead of names. Only the 
researchers will know what participants’ number is and we will lock that information up with a lock and key. 
It will not be shared with or given to anyone and will be concealed in publication of a research article.  
Sharing the Results 
The knowledge that we get from doing this research will be shared with you through journal publication to 
be widely available to the public in order that other interested people may learn from our research. However, 
the privacy and confidentiality of the participants will be maintained in the results. 
Right to Refuse or Withdraw 
Participants do not have to take part in this research if they do not wish to do so and refusing to participate 
will not affect your treatment at this clinic in any way.  Participants will still have all the benefits that they 
would otherwise have at this clinic. Participants may stop participating in the research at any time without 
losing any of their rights as a patient here. Participants’ treatment at this clinic/hospital will not be affected 
in any way. 
Who to Contact 
If you wish to ask questions later, you may contact any of the following:  
Ms. Sameera Shafiq 
Address: Office A212, Department of Psychology, Ibn-e-Khaldun Block, Department of Psychology, 
University of Gujrat, Gujrat.  
Cell: +923345116648 
Email: sameera.shafiq@uog.edu.pk 
 
This proposal has been reviewed and approved by Institutional Review Board (IRB) UOG/ORIC/2022/393, 
UOG which is a committee whose task is to make sure that research participants are protected from harm.  
 
 


References 
Akhtar, A., Rahman, A., Husain, M., Chaudhry, I. B., Duddu, V., & Husain, N. (2010). Multidimensional 
scale of perceived social support: psychometric properties in a South Asian population. Journal of 
Obstetrics and Gynaecology Research, 36(4), 845-851. 
Bodenmann, G. (2008). Dyadisches Coping Inventar: Test manual [Dyadic Coping Inventory: Test manual]. 
Bern, Switzerland: Huber. 
Choudhry, F. R., Al-Worafi, Y. M., Akram, B., Ahmed, M. A., Anwar ul Haq, M., Khan, T. M., ... & 
Golden, K. J. (2018). Factor structure of urdu version of the flourishing scale. Frontiers in 
psychology, 9, 1513. 
Diener, E., Wirtz, D., Tov, W., Kim-Prieto, C., Choi, D., Oishi, S., & Biswas-Diener, R. (2009). New 
measures of well-being: Flourishing and positive and negative feelings. Social Indicators Research, 39, 
247-266. 
Lodhi, F. S., Raza, O., Montazeri, A., Nedjat, S., Yaseri, M., & Holakouie-Naieni, K. (2017). Psychometric 
properties of the Urdu version of the World Health Organization's quality of life questionnaire 
(WHOQOL-BREF). Medical journal of the Islamic Republic of Iran, 31, 129. 
Shafiq, S., Bano, Z., Randhawa, S. S., Khan, K. H., Muhammad, Q. U., & Muhammad, A. (2022). 
Effectiveness of adapted cognitive behaviour therapy for dysthymia: An evidence based case 
study. JPMA. The Journal of the Pakistan Medical Association, 72(3), 554-556. 
Shujja, S., Adil, A., Randall, A. K., Bodenmann, G., & Malik, F. (2020). Psychometric properties and 
validity of Dyadic Coping Inventory-Urdu Version for use in Pakistan. Interpersona: An International 
Journal on Personal Relationships, 14(2), 183-199. 
Whoqol Group. (1998). Development of the World Health Organization WHOQOL-BREF quality of life 
assessment. Psychological medicine, 28(3), 551-558. 
Zimet, G.D., Dahlem, N.W., Zimet, S.G. & Farley, G.K. (1988). The Multidimensional Scale of Perceived 
Social Support. Journal of Personality Assessment, 52, 30-41. 
 
 
 


 
 
                                
                                                           Informed Consent Form  
                                      Health Care Professional (Consultant Gynaecologist) 
 
 
Research Project: "The Effectiveness of Psychopharmacological Intervention versus Cognitive Behavioural 
Couple Therapy and Their Combination in Perinatal Distressed Couples: A Randomized Clinical Trial"  
Principal Investigator: Ms Sameera Shafiq (Ph.D. Scholar and Lecturer) 
Department of Psychology, University of Gujrat, Gujrat, Pakistan. 
 
Unique Protocol ID: UOG/ORIC/2022/393  
Brief Title: Cognitive Behavioral Couple Therapy for Perinatal Distress  
Registration: NCT06001021 
Initial Registration: 26th June, 2023. 
Initial Approval and Public Release Date: 13th August, 2023. 
Sponsor/Funder: Nil 
 
PART II: Certificate of Consent 
I have read the foregoing information, or it has been read to me. I have had the opportunity to ask questions 
about it and any questions that I have asked have been answered to my satisfaction.  I consent voluntarily to 
participate as a health care professional (Consultant Gynaecologist) in this research. 
 
Name of a Consultant Gynaecologist: ___________________________  
 
 
 
Signature and Stamp of Consultant Gynaecologist ________________ 
 
  
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
                               Informed Consent Form  
                                      Distressed Couples (High-Risk) in Perinatal Period 
 
Research Project: "The Effectiveness of Psychopharmacological Intervention versus Cognitive Behavioural 
Couple Therapy and Their Combination in Perinatal Distressed Couples: A Randomized Clinical Trial"  
Principal Investigator: Ms Sameera Shafiq (Ph.D. Scholar and Lecturer) 
Department of Psychology, University of Gujrat, Gujrat, Pakistan 
Unique Protocol ID: UOG/ORIC/2022/393  
Brief Title: Cognitive Behavioral Couple Therapy for Perinatal Distress  
Registration: NCT06001021 
Initial Registration: 26th June, 2023. 
Initial Approval and Public Release Date: 13th August, 2023. 
Sponsor/Funder: Nil 
The informed consent form consists of two parts:  
• 
Information Sheet (to share information about the research with you) 
• 
Certificate of Consent (for signatures if you agree to take part) 
PART I: Information Sheet 
Introduction 
I am Ms Sameera Shafiq/Mrs. Sameera Ahmed conducting a research study on couple’s perinatal distress. I 
am going to give you information and invite you to be part of this research. Before you decide, you can talk 
to anyone (especially your gynaecologist) you feel comfortable with about the research. There may be some 
words that you do not understand. Please ask me to stop as we go through the information and I will take 
time to explain.  If you have questions later, you can ask them of me, the gynaecologist or the staff. 
Purpose of the Research 
Perinatal Distress (such as depression and/or anxiety) is a growing concern nowadays and is observed in 
couples (wives and husbands) during antenatal and postnatal period. It might effect the family and the 
foetus-infant badly if left unnoticed. NICE guidelines have recommended screening and treating perinatal 
women for depression and anxiety. Researches showed that perinatal distress can be treated with 
psychotropic medications, cognitive behavioural therapy and/or a combination of both. The reason we are 
doing this research is to find out if the medications (antidepressant and/or anxiolytics) are better than 
cognitive behavioural therapy or combination of both as a treatment for perinatal distress in the couples.   
Type of Research Intervention 
This research study involves the following treatments 
6) Medications (antidepressants and/or anti-anxiolytics). 
7) Cognitive Behavioural Therapy without Zikr. 
8) Cognitive Behavioural Therapy with Zikr. 
9) Combination of medications and cognitive behavioural therapy. 
10) Combination of medications, cognitive behavioural therapy, and zikr. 
 


Participant Selection 
We are inviting all women (4th month to 8th month in antenatal period; after a week till one year of a child in 
postnatal period) and selecting willing couples with perinatal distress (high-risk) who attends gynaecology of 
the hospital to participate in the research with the treatment offered for free. The age range will be between 
19 to 45 years.  
Voluntary Participation 
Your participation in this research is entirely voluntary. It is your choice whether to participate or not. 
Whether you choose to participate or not, all the services you receive at this clinic will continue and nothing 
will change. If you choose not to participate in this research project, you will offer the treatment that is 
routinely offered in this clinic/hospital. You may change your mind later and stop participating even if you 
agreed earlier. 
Information on the Trial Medicine [Antidepressants and Anxiolytics] 
1) The antidepressants and/or anxiolytics safe in antenatal (2nd and 3rd trimester) and postnatal period will be 
prescribed.  
2) Anxiolytics used to control symptoms of anxiety without serious impairment of normal physical or mental 
function. Antidepressants reduce mood swings and improve overall wellbeing. 
3) Some common side effects of antidepressants include feeling agitated, shaky, indigestion and stomach 
aches, diarrhoea or constipation, loss of appetite, dizziness, not sleeping well, or feeling very sleepy, 
headaches. Some short-term side effects of anxiolytics can include Low heart rate, Low blood pressure, Irregular 
breathing, Confusion, Dizziness, Nausea. These side effects are temporary and will be settled down in two weeks 
and the medication will start working for normalization of mood and/or reduction of anxiety.  
Procedures and Protocol 
We will ask you to select one of your preferred treatment modes out of the following 
6) Medications (antidepressants and/or anti-anxiolytics). 
7) Cognitive Behavioural Therapy without Zikr. 
8) Cognitive Behavioural Therapy with Zikr. 
9) Combination of medications and cognitive behavioural therapy. 
10) Combination of medications, cognitive behavioural therapy, and Zikr. 
A list of willing participants will be prepared. Each participant will have one in five chances of getting the 
preferred treatment mode. There will be two groups (experimental and control). To put people into one of 
the two groups, we will select by chance as for instance by random number generated by a research assistant.  
Participants will not know to which group they actually belong. This information will be in our files, but we 
will not look at these files until after the research is finished. This is the best way we have for testing without 
being influenced by what we think or hope might happen. We will then compare which of the two has the 
best results. If there is anything you are concerned about or that is bothering you about the research please 
talk to me or my research assistant or your gynaecologist.  
A placebo or inactive medicine looks like real medicine but it is not. It is a dummy or pretend medicine. It 
has no effect on a person because it has no real medicine in it. We want to know whether medicine is good, 
we give some people the medicine and some people the pretend or dummy medicine. For the research to be 
good, it is important that you do not know whether you have been given the real medicine or the pretend or 
dummy medicine.  This is one of the best ways we have for knowing what the medicine we are testing really 
does. But the participants given placebo will be informed in the end of the study and will be given treatment 
with medication.  
Description of the Process 
During the research a couple has to make ten visits to attend ten sessions in the hospital. 


 In the first visit, rapport will be build and pre-test assessment will be done in the following two 
approaches 
Quantitative Approach 
 Indigenously developed Parental Perinatal Distress Scale (PPDS). 
 Urdu version (Akhtar, Rahman, Husain, Chaudhry, Duddu,… & Husain, 2010) of Multidimensional 
Social Support Scale (Zimet, Dahlem, Zimet, & Farley, 1988).  
 Urdu version (Shujja, Adil, Randall, Bodenmann, & Malik, 2020) of Dyadic Coping Inventory 
(Bodenmann, 2008).  
 Urdu version (Choudhry, Al-Worafi, Akram, Ahmed, Anwar ul Haq, Khan,…  & Golden, 2018) of 
Flourishing Scale (Diener, Wirtz, Tov, Kim-Prieto, Choi, Oishi, & Biswas-Diener, 2009).  
 Urdu version (Lodhi, Raza, Montazeri, Nedjat, Yaseri, & Holakouie-Naieni, 2017) of World Health 
Organization’s Quality of Life Brief (WHOQOL Group, 1998).  
Qualitative Approach 
 Semi-structured interview will be conducted to explore the present stressors and expectations and 
perceptions about effectivity of treatments for perinatal distress among couples.  
Group 1 will be given medications or placebo for two weeks and/or for four to five weeks maximum. They 
have to visit after two weeks for post-test assessment. As explained before, neither you nor we will know 
whether you have received the medicine or the placebo. But in the end placebo participants will be debriefed 
and will be continued with real medication. Consultant gynaecologist will prescribe medication after 
thorough risk-benefit evaluation. 
Group 2, Group 3, and Group 4 will continue the following sessions 
 In the second session, you will be psycho-educated for perinatal period distress, couples’ physical 
and mental health and impact on the foetus-infant, prevalence of depression and anxiety and 
significance of identification. Progressive muscle relaxation exercise will be carried out along with 
deep breathing. Feedback on the session will be taken. 
 In the third session, you will be psycho-educated for the theoretical model of cognitive behavioural 
couple therapy with some historical highlights and empirical standing. Thought log will be given for 
homework. Feedback for deep breathing and progressive muscle relaxation will be carried out.  
 In the fourth, fifth, sixth, seventh, eighth and ninth session, feedback will be taken on homework and 
session. Various techniques of Cognitive Behavioural Couple Therapy will be applied based on the 
nature and contents of identified precipitating, perpetuating, and present stressors. In addition, 
relevant techniques will be incorporated from other modalities with eclecticism. Tasbeeh (see Shafiq 
et al., 2022) in Zikr will be given to group 3 and group 5 who opted for it in screening process.  
 In the tenth visit, feedback on session and homework will be taken. post-test assessment will be done 
in the following two approaches 
Group 5 will be exposed to one of the two conditions. 50% couples will get placebo and 50% will receive 
the routine treatment care with no intervention. However, after the completion of the research, this waitlist 
group (control) will be briefed and will be delivered with intervention mode of treatment.  
Quantitative Approach 
 Indigenously developed Parental Perinatal Distress Scale (PPDS) 
 Urdu version (Akhtar, Rahman, Husain, Chaudhry, Duddu, & Husain, 2010) of Multidimensional 
Social Support Scale (Zimet, Dahlem, Zimet, & Farley, 1988).  
 Urdu version (Shujja, Adil, Randall, Bodenmann, & Malik, 2020) of Dyadic Coping Inventory 
(Bodenmann, 2008).  
 Urdu version (Choudhry, Al-Worafi, Akram, Ahmed, Anwar ul Haq, Khan, … & Golden, 2018) of 
Flourishing Scale (Diener, Wirtz, Tov, Kim-Prieto, Choi, Oishi, & Biswas-Diener, 2009).  
 Urdu version (Lodhi, Raza, Montazeri, Nedjat, Yaseri, & Holakouie-Naieni, 2017) of World Health 
Organization’s Quality of Life Brief (WHOQOL Group, 1998).  


Qualitative Approach 
 Semi-structured interview will be conducted to explore the present stressors and expectations and 
perceptions about effectivity of treatments for perinatal distress among couples.  
Duration  
The research takes place over from 15th August, 2023 to 30th October, 2023. Screening with PPDS will be 
carried out on the couples who visit gynaecological ward of the hospital in August. After screening, 
enrolment, and signed informed consent, it will be necessary for participants to come to the clinic/hospital 
for 10 days in total, for one hour session each day in last week of August (two days per week, each for one 
hour) till September. A follow-up visit after two weeks in October is compulsory. In a follow-up qualitative 
approach of interviewing will be used.  
Reimbursements 
We will give you [PKR. 500/-] to pay for your travel to the clinic. You will not be given any other money or 
gifts to take part in this research. 
Confidentiality 
The information that we collect from this research project will be kept confidential. Information about you 
that will be collected during the research will be put away and no-one but the researchers will be able to see 
it. Any information about you will have a number on it instead of your name. Only the researchers will know 
what your number is and we will lock that information up with a lock and key. It will not be shared with or 
given to anyone and will  be concealed in publication of a research article.  
Sharing the Results 
The knowledge that we get from doing this research will be shared with you through journal publication to 
be widely available to the public in order that other interested people may learn from our research. However, 
the privacy and confidentiality of the participants will be maintained in the results.  
Right to Refuse or Withdraw 
You do not have to take part in this research if you do not wish to do so and refusing to participate will not 
affect your treatment at this clinic in any way.  You will still have all the benefits that you would otherwise 
have at this clinic. You may stop participating in the research at any time that you wish without losing any of 
your rights as a patient here. Your treatment at this clinic will not be affected in any way. 
Who to Contact 
If you wish to ask questions later, you may contact any of the following:  
Ms. Sameera Shafiq 
Address: Office A212, Department of Psychology, Ibn-e-Khaldun Block, Department of Psychology, 
University of Gujrat, Gujrat.  
Cell: 03345116648 
Email: sameera.shafiq@uog.edu.pk 
 
This proposal has been reviewed and approved by Institutional Review Board (IRB) reference no. 
UOG/ORIC/2022/393, UOG which is a committee whose task is to make sure that research participants are 
protected from harm.  
References 
Akhtar, A., Rahman, A., Husain, M., Chaudhry, I. B., Duddu, V., & Husain, N. (2010). Multidimensional scale of 
perceived social support: psychometric properties in a South Asian population. Journal of Obstetrics and 
Gynaecology Research, 36(4), 845-851. 
Bodenmann, G. (2008). Dyadisches Coping Inventar: Test manual [Dyadic Coping Inventory: Test manual]. Bern, 
Switzerland: Huber. 


Choudhry, F. R., Al-Worafi, Y. M., Akram, B., Ahmed, M. A., Anwar ul Haq, M., Khan, T. M., ... & Golden, K. J. 
(2018). Factor structure of urdu version of the flourishing scale. Frontiers in psychology, 9, 1513. 
Diener, E., Wirtz, D., Tov, W., Kim-Prieto, C., Choi, D., Oishi, S., & Biswas-Diener, R. (2009). New measures of 
well-being: Flourishing and positive and negative feelings. Social Indicators Research, 39, 247-266. 
Lodhi, F. S., Raza, O., Montazeri, A., Nedjat, S., Yaseri, M., & Holakouie-Naieni, K. (2017). Psychometric properties 
of the Urdu version of the World Health Organization's quality of life questionnaire (WHOQOL-
BREF). Medical journal of the Islamic Republic of Iran, 31, 129. 
Shafiq, S., Bano, Z., Randhawa, S. S., Khan, K. H., Muhammad, Q. U., & Muhammad, A. (2022). Effectiveness of 
adapted cognitive behaviour therapy for dysthymia: An evidence based case study. JPMA. The Journal of the 
Pakistan Medical Association, 72(3), 554-556. 
Shujja, S., Adil, A., Randall, A. K., Bodenmann, G., & Malik, F. (2020). Psychometric properties and validity of 
Dyadic Coping Inventory-Urdu Version for use in Pakistan. Interpersona: An International Journal on Personal 
Relationships, 14(2), 183-199. 
Whoqol Group. (1998). Development of the World Health Organization WHOQOL-BREF quality of life 
assessment. Psychological medicine, 28(3), 551-558. 
Zimet, G.D., Dahlem, N.W., Zimet, S.G. & Farley, G.K. (1988). The Multidimensional Scale of Perceived Social 
Support. Journal of Personality Assessment, 52, 30-41. 
 
 
 


                                                           Informed Consent Form  
                                      High Risk for Distress Couples in Perinatal Period 
 
 
Research Project: "The Effectiveness of Psychopharmacological Intervention versus Cognitive Behavioural 
Couple Therapy and Their Combination in Perinatal Distressed Couples: A Randomized Clinical Trial"  
Principal Investigator: Ms Sameera Shafiq (Ph.D. Scholar and Lecturer) 
Department of Psychology, University of Gujrat, Gujrat, Pakistan. 
 
Brief Title: Cognitive Behavioral Couple Therapy for Perinatal Distress  
Registration: NCT06001021 
Initial Registration: 26th June, 2023. 
Initial Approval and Public Release Date: 13th August, 2023. 
Sponsor/Funder: Nil 
 
PART II: Certificate of Consent 
We have read the foregoing information, or it has been read to me. We have had the opportunity to ask 
questions about it and any questions that we have asked have been answered to my satisfaction.  We consent 
voluntarily to participate in this research. 
 
Names (optional): ___________________________ 
 
 
 
 
Signatures ________________ 
 
  
 
 
 
 
 
 

Prot_000.pdf: 
1 
 
 
The Effectiveness of Psychopharmacological Intervention versus Cognitive Behavioral 
Couple Therapy and their Combination in Perinatal Distressed Couples:  
A Randomized Clinical Trial 
 
Unique Protocol ID: UOG/ORIC/2022/393  
Brief Title: Cognitive Behavioral Couple Therapy for Perinatal Distress  
Official Title: The Effectiveness of Psychopharmacological Intervention Versus Cognitive 
Behavioural Couple Therapy and Their Combination in Perinatal Distressed Couples: A 
Randomized Clinical Trial 
Registration: NCT06001021 
Initial Registration: 26th June, 2023. 
Initial Approval and Public Release Date: 13th August, 2023. 
 
Sponsor/Funder: Nill 
 
Sameera Shafiq1* 
*Correspondence: sameera.shafiq@uog.edu.pk; sameerashafiq@yahoo.com  
1Lecturer and Ph. D. Scholar, Department of Psychology, University of Gujrat (Gujrat), 
Pakistan.  
+923345116648; +9253-3643331, 205(ext) 
 
 


2 
 
Abstract 
Perinatal distress as manifested in the symptomology of Major Depressive Disorder and 
Generalized Anxiety Disorder in mothers has detrimental effects on foetus and infants. Keeping 
in consideration the well-being of foetus and infant, the present study has focused on provision 
of treatment to the screened high-risk distresses mothers along with inclusion of fathers visiting 
obstetrics/gynaecology wards in the hospitals. The present randomized clinical trial will be 
carried out on nth participants (Nth couples), recruited from the Maternity Clinic, Islamabad and 
Qamar Maternity Hospital, Gujar Khan, Pakistan.  Randomization will be carried out in this 
completely randomized experimental research design. The multi-arms parallel group trial will be 
conceded. The participants will be randomly allocated either to intervention groups or waitlist 
control groups with the use of online random number generator calculator. The five intervention 
arms will be Psychopharmacological intervention, Cognitive Behavioral Couple Therapy 
(CBCT), CBCT with Zikr, combination of psychopharmacology with CBCT, and combination of 
psychopharmacology with CBCT along with Zikr. The medicines will be prescribed by a 
gynaecologist after thorough evaluation of risk and benefits. Ten therapeutic sessions (60 
minutes) by the investigator will be administered in group. The waitlist control group will 
receive either a placebo or no intervention which implies that they will carry out routine 
gynaecological check-ups. A sum of scores obtained with Major Depressive Disorder Subscale 
(MDDS) and Generalized Anxiety Disorder Subscale (GADS) of Parental Perinatal Distress 
Scale (PPDS) will used to assess levels of perinatal depression and perinatal anxiety, collectively 
named perinatal distress in couples before and after intervention.  In addition, Urdu versions of 
Dyadic Coping Inventory (DCI), Multidimensional Scale for Perceived Social Support (MSPSS), 
Flourishing Scale (FS), and World Health Organization Quality of Life Scale-WHOQOL-BREF 
will be used to assess coping strategies, social support, wellbeing, and perceived quality of life at 
pre-test and post-test.  Based on adjustment of baseline pre-test total scores for distress (anxiety 
and depression) and monthly income, ANCOVA will be applied to assess the impact after 
treatment for five intervention groups as compared to two control group. It will be fruitful to 
deliver mental health services in antenatal and postnatal periods for alleviation of mental health 
and prevention of psychopathological disorders in high-risk couples while screening visitors 
coming in obstetrics and gynaecological wards for routine check-ups in Pakistan.  
 
 


3 
 
 
Background  
The mental disorders such as depression, anxiety, bipolar disorder, and psychosis play significant 
role in influencing mother’s and baby’s health during pregnancy and postpartum [1]. Child’s 
cognitive and physical development during pregnancy and after delivery is effected by mother’s 
mental health [2-4]. These researches signify the importance of early screening and efficacious 
management for the symptoms of mania, anxiety, and depression in women during perinatal 
women [1].  The cognitive-behavioural model comprehends the experiences of depression in 
reciprocal interaction between thoughts, emotions, and behaviours in a peculiar context thereby 
elaborating their etiopathogenetic contributions. It further expounds these interpretations into the 
development of clinically effective techniques aimed at reduction of the problematic expression 
of the symptoms [5]. This model is also empirically effective for treating anxiety disorders [6]. 
The cognitive and behavioural techniques have long-term effects in reducing the levels of 
depression and the anxiety disorders [7]. Nevertheless, fathers suffering with depression and 
anxiety during perinatal period receive reduction in the symptoms by use of cognitive behavioral 
therapy in group [8]. 
The prevalence for perinatal depression ranged between 10% and 20% for women impacting not 
only them but also their husbands and children [9]. A high prevalence rate 29.2% and 24.4% is 
observed for antenatal and postnatal anxiety in women [10]. Paternal perinatal anxiety was found 
to be 10.69% [11] whereas average paternal perinatal depression was reported to be 9.25% [12]. 
Thus, treatment plan has to be inclusive to the fathers as well as to the mothers for better 
wellbeing of foetus and baby. Interventions with psychoeducation, communication training, and 
behavioral activation benefit women when husbands are involved in the therapeutic treatment 
[9]. Therefore, gaps exist in understanding and treatment of perinatal depression and perinatal 
anxiety in women [13]. The effective treatment and prevention of postpartum depression 
included studies based on randomised controlled trials with investigation of psychosocial factors 
and counselling interventions. The randomized controlled trials used lowest effective dose for 
management of depression and anxiety symptoms during antenatal and postnatal period after 
conducting a risk-benefit analyses based on individual cases for treatment. For future trial 
researches, it has been recommended that involvement of fathers along with mothers and focus 
on economic constraints in low income settings could yield beneficial results in provision of 
mental health facilities [14]. 
Cognitive Behavioral Couple Therapy (CBCT) is the offshoot of Cognitive Behavior Therapy 
(CBT); the amalgam in the cognitive- and behavior therapies to focus on dysfunctional 


4 
 
relationships between husband and wife. Healthy functioning is practiced by structure of the 
therapy process, assessment and intervention plan with focus on goal setting by a therapist to 
eliminate distress and enhance wellness and satisfaction [15-16]. The third wave in couple 
therapy showed integration of meditation, religiosity and spirituality for the improvement of the 
quality of relationship between husband and wife [17-19]. Recently, empirical evidences of 
randomized controlled trial in meditation have been found to be effective improving 
electroencephalograph (EEG) in brain waves for the reduction of psychological distress [20]. The 
present study has focused on application of CBCT because Patterson (2017) [21] has found 
CBCT to be empirically sound for providing experimentation based evidences than any other 
therapeutic intervention used with couples. In order to assess efficacy of CBCT among 
perinatal couples, a randomized clinical trial will be used. According to James, Rao, and Granger 
[22], randomized clinical trials are empirically proven methodology of reliably controlling the 
confounding variables and presenting a plausible association between selection of treatment 
option and well-being outcome. The Perinatal Distress Model signifies the crucial role played by 
socio-cultural traditional explanations for distress in pregnancy and after birth for women in 
Pakistan [23]. Therefore, one cannot ignore the role of socio-cultural practices for healing in 
perinatal women. Zikr is considered instrumental in provision of improved mental and physical 
health among Muslims [24-25]. The word Zikr is interchangeably used with word of medication 
or more precisely Islamic meditation or mindfulness.  
Meditation is defined as the individual’s ability “to focus their attention on a single object, such 
as an image or a mantra” [26]. Mediation and mindfulness is linked and considered to be the 
synonyms of one another that play a crucial role in decline of psychological distress [27-30]. 
“Mindfulness has been described as a practice of learning to focus attention on moment-by-
moment experience with an attitude of curiosity, openness, and acceptance” [31] (Marchand, 
2012, p. 233). Therefore, the elements of meditation or mindfulness implied focus on experience, 
sensation, image, mantra, thought and gradual enhancement of that focus of attention, 
transforming into the practice of concentration, eliminating the thoughts and gaining relaxation. 
The mindfulness or more precisely meditation in Pakistani culture is visible in religio-spiritual 
context of Islam.  
Muraqabah in Islam is conceptually akin to meditation or mindfulness technique, except they 
differed in use of Zikr or mantras [32-33]. The meanings of mediation in Islam are diverse 
ranging from focus on remembrance of God, Dhikr/Zikr, by vocalization of Quranic verses, or 
Divine Names to formal ritualized manner of performing prayers five times a day [34]. Zikr, 
remembrance of God, has been found to be effective in reduction of distress, pain and suffering 


5 
 
in various physical and psychological disorders [35-38]. The present research has focused on use 
of Professor Ahmed Rafique Akhtar’s approach towards Zikr, based on two Quranic verses: 
Translation: “Remember Allah like your remembrance of your fathers or with greater 
remembrance” (Al Quran, Surah Bakarah, Verse 200). Translation: “And when I am ill, it is He 
who cures me” (Al Quran, Surah Shu’ara, Verse 80).  
In order to make Zikr one’s habit, it is necessary to initiate the recitation without concentration 
because in this way one remember Allah as he tries to remember his beloved relatives and 
significant others with affection and nostalgia. Ones it become your habitual memorization and 
one attain regularity in it; it can be imparted to others. The Zikr can be recited without ablution 
(wozu), through tongue, casually, informally, performing various tasks, such as watching 
television, listening to music, and talking etc. The imparting of Zikr is exclusively contingent on 
the values of the individuals. It is neither recited on someone else behalf nor without personal 
willingness. It is intended to be recited regularly for the sake of God only not for any worldly 
gain or aim. The term Zikr is used instead of meditation because there is no condition of focused 
attention or concentration in the remembrance of God through His Names especially Ya Salam 
(The Peace Giver), Ya Momin (The Faith Giver), Ya Allah (300 times per day); Ya Rehman (The 
Merciful), Ya Raheem (The Compassionate), Ya Kareem (The Generous) (300 times per day); 
Lahaolawala quwata illah billah (There is no might nor power except with Allah, 300 times per 
day) to name a few. The quantity for recitation is adjustable according to the person’s capacities. 
Care must be taken in recitation of either Ya Salam or Ya Momin. The names starting with S 
should avoid recitation of Ya Momin and the names starting with M should refrain from oration 
of ration of a Salam [39-40]. Either Ya Salam (100 times) or Ya Momin (100 times) and Ya 
Rehman (100 times) along with Lahaolawala quwata illah billah (100 times) and Ayat Kareema 
(40 times) were found effective in reducing dysthymic symptomology in a patient when imparted 
in junction to CBT [41]. Numerous researches have posited the efficacy of Zikr in reducing 
perinatal depression and perinatal anxiety [42-44]. 
The values and preferences of the clients have to be considered and respected while providing the 
treatment with cognitive behavior therapy [45]. This basic principle in Beck’s Approach to 
Cognitive Behavior Therapy, undermines the bifurcations in CBT practice by renaming it as 
“Religious Cognitive-Behavior Therapy” [46-47], “Secular and Religious versions of Cognitive 
Behavior Therapy” [48], “Religious and Nonreligious Cognitive-Behavioral Therapy” [49], 
“Religion-Adapted Cognitive Behavioral Therapy” [50], “Religious vs. conventional cognitive 
behavioral therapy” [51] and [41, 52].  


6 
 
A systematic review of ten randomized controlled trials aimed at comparison of combined 
treatment of medicines and CBT with CBT alone for broad spectrum anxiety disorders was 
carried out. The findings posited non superior effectiveness of combined CBT with medicine 
treatment and CBT monotherapy treatment in anxiety disorders with respect to effect size [53]. 
Similar findings in another review indicated that combination of anxiolytics and CBT for 
different kinds of anxiety disorders are not better than monotherapy of medicine and CBT [54]. 
However, meta-analysis of psychopharmacological and psychological intervention (specifically 
CBT) showed significant improvement in perinatal depression with effect size Hedges’ g 0.65 
[55]. Additional meta-analyses revealed effectivity of CBT [56-58] and antidepressants [59] in 
perinatal depressed women. But placebo controlled trials did not reveal efficacious differences 
for medications in depressed women during antenatal and postpartum period [60-61].  
In Pakistan, scarce randomized controlled trials (RCT) have been carried out to reduce prenatal 
anxiety [62] and perinatal depression [63-64] in women via psychotherapeutic interventions. 
However, a few researches have reported about the effectivity of Zikr in decreasing antenatal 
depression and anxiety in pregnant women in Indonesia [65-66].  Therefore, a gap existed in 
evaluation of efficacy of psychopharmacological approach injunction with psychological 
intervention and Zikr for reduction of symptomology of perinatal distress in women and men 
(spouse). Hence, the primary objective of this research was to evaluate the impact of treatment 
with medication, CBCT (conditions: with or without Zikr), and their combination to decrease 
symptoms of distress (depression and anxiety) assessed by using the Major Depressive Disorder 
Subscale and Generalized Anxiety Subscale of Parental Perinatal Distress Scale in the fourth 
month and onward pregnancy till one year after childbirth in high-risk couples between 
intervention and control groups (primary outcome).  
Objectives of the Study 
The primary objective of the present study will be: 
 To evaluate effectivity of psychopharmacological treatment, CBCT (with or without 
Zikr), and combined medicine-CBCT (with or without Zikr) interventions be in reducing 
symptoms of distress and improving quality of life, social support, wellbeing, and coping 
strategies among couples during the perinatal period at the post-test level as compared to 
the waitlist control group in the high risk couples for perinatal distress.  
The secondary objective of the present study will be: 
 To report occurrence of side-effects after the use of psychotropic medications in in the 
high risk couples for perinatal distress. 


7 
 
 To report occurrence of any adverse events after the use of psychotropic medications in 
in the high risk couples for perinatal distress. 
Hypotheses of the Study 
The presence of mix findings for efficacy of different interventions instigated sequential 
superiority-equivalence approach in hypotheses. The primary hypotheses based on the 
superiority trial approach of the study will be: 
 There will be significant differences in psychopharmacology on total scores of 
perinatal distress between the experimental and wait list-control groups. 
 There will be significant differences in CBCT on total scores of dyadic coping 
strategies between the experimental and wait list-control group.  
 There will be significant differences in CBCT with Zikr on total scores of perceived 
social support between the experimental and wait list-control groups.  
 There will be significant differences for combined psychopharmacology, and CBT 
with Zikr on total scores of wellbeing between experimental and wait list-control 
group. 
 There will be significant differences for combined psychopharmacology, and CBT 
without Zikr) on total scores of perceived quality of life between experimental and 
wait list-control group. 
The secondary hypothesis based on the equivalence trial approach of the present study will be: 
 Combined intervention with psychopharmacology and cognitive behavioural therapy 
(with or without Zikr) will not be more effective than only psychopharmacology and only 
CBCT in treating distress in intervention group.   
Methodology  
The study was approved by Institutional Review Board (IRB), University of Gujrat, with 
reference no: UOG/ORIC/2022/393. After initial registration dated 26th June, 2023, the trial 
protocol was approved on 13th August, 2023 by ClinicalTrials.gov, reference no: NCT06001021, 
to start the enrolment and sampling. The research will take place from 15th August, 2023 to 30th 
September, 2023; with two follow-ups in October, 2023, each conducted after a two-week gap.  
 
Study Design 
The completely randomized design (CRD) is used to assign sample units to different treatment 
groups [67-69]. Each sample unit is considered uniform (all were selected at high risk with 
inclusion criteria) with respect to the presence of the perinatal distress.  Therefore, the present 


8 
 
study will be multi-arm parallel group randomized trial [70-71]. The present double-blind 
randomized controlled clinical trial will contain five parallel arms of interventions and a waitlist 
control arm (conditions: either with administration of a placebo or no intervention). The 
participants and a research assistant will be blinded for allocation of the participants to the 
parallel arms for maintaining the principle of randomization.  
The study design is sequential superiority-equivalence trial [72-73]. Superiority trial hypotheses 
apply statistical test to consider evidence for a treatment to be better than the control either with 
no treatment or with placebo. Equivalence trial hypotheses apply statistical test to exhibit that 
any two treatments are not too different in characteristics, and any limited differences are 
operationally defined in a clinical manner [74]. Recruitment will be carried out from 15th August, 
2023 to 26th August, 2023 in a Maternity Clinic Islamabad and Qamar Maternity Hospital in 
Gujar Khan, Pakistan. The participants visiting obstetrics/gynaecological clinic, hospital will be 
identified via screening carried out by the investigator and the research assistant. They will be 
assessed according to the eligibility criteria and written informed consent will be sorted. The n% 
of participants fulfilling inclusion eligibility criteria and giving consent to take part in the study 
will be up taken strategically  receiving recruitment to be randomized into intervention and 
control groups of the RCT. 
Sample Size 
The sample size will be calculated manually by using a formula [75]: 
 
Z1-α/22 p (1-p) 
d2 
Where, Z1-α/2 is considered a standard normal variate; p is the expected proportion (prevalence) 
of perinatal distress in the population based on the study of Smythe et al., [76]; and d is the 
absolute error, decided by the researcher as 0.10 based on the suggestion by the experts [77-78]. 
The researcher has decided absolute error to be fixed at 0.10 due to lack of financial resources 
and economy of time. 
The sample size calculated with above formula will be used and 7 participants will be considered 
for each arm. Since, the present study considers couples, for couples per arm of five intervention 
groups and one control group of RCT will be taken. Hence, it implies that 4 couples in each arm 
will be sufficient for the performance of the RCT to evaluate effectivity of CBCT in the main 
study. Nevertheless, a sample size of 15 participants in each arm is considered based on 
statistical considerations of sample size in randomized controlled trials [79]. Therefore, five 
intervention groups and one control arm necessitates recruitment of a total of 90 participants in a 


9 
 
study. In addition, 10% additional sample size is kept in the present study to avoid issues of loss 
of the participants in post-test assessment and follow-ups [80-81]. Formula for adjusted sample 
size with 10% dropout rate [82] is given below: 
 
Adjusted Sample Size = calculated sample size divided by (1-dropout rate) 
The adjusted sample size is 8 participants. Since, the present research will be conducted on the 
couples, 4 couples (8 participants) will be added to get adjusted sample size with 10% dropout 
forecast to actual sample size calculated for each arm that is four couples (8 participants). 
Conclusively, 16 participants will be recruited with randomization in a present clinical trial in 
each five arms of intervention group (Psychopharmacological intervention arm; CBCT without 
Zikr arm; CBCT with Zikr arm; combined psychopharmacological intervention with CBCT 
without Zikr arm; and combined psychopharmacological intervention with CBCT with Zikr arm) 
and a control group (either with placebo arm or no intervention arm). The sample size will be of 
96 participants (48 couples) in present RCT.  
Inclusion/Exclusion Criteria 
Inclusion Criteria for the participants will focus on: couples age range 19 to 45 years; fourth 
month of pregnancy till the seventh month of the antenatal period, One week after delivery/birth 
till one year of a child in the postnatal period; screened by Major Depressive Disorder Subscale 
and Generalized Anxiety Disorder Subscale of Parental Perinatal Distress Scale as high-risk 
couples, with perinatal depression (cut-off score 29 to 42) and perinatal anxiety (cut-off score 17 
to 24), and their comorbidity (cut-off score ≥ 40 and ≥ 20 on both subscales respectively; total 
sum of scores on both MDDS and GADS ≥45 for high risk perinatal distress; Dose requirements 
in any one or in combination of the antidepressant and/or anxiolytic, such as escitalopram (5-10 
mg), sertraline (12.5-25 mg), and/or alprazolam (0.25-0.50 mg) per day; Wives accompanied by 
their husbands; husband is earning monthly income; couple is learned; Willingness to participate 
as a couple in the study; No physical disorder is present; No intellectual disability is present; no 
history of miscarriage or infant mortality in one year; no history of psychiatric disorder or 
psychotropic drug intakes. Exclusion Criteria will focus on: age range below 19 and above 45 
years; unwilling couples or any one, to participate in the study; wife and/or couple is in an 
emergency; wife and/or couple has unstable mental health; wife accompanied by close relatives 
other than a spouse; wife in the first week of delivery; ; low score on either or both MDDS and 
GADS than inclusion criteria for high risk perinatal distress; dose requirements in any one of the 
antidepressant and/or anxiolytic, such as escitalopram (>10 mg), sertraline (>25 mg), and/or 
alprazolam (>0.50 mg) per day; husband is not earning monthly income and other family 


10 
 
members are the source of income; either wife or husband is illiterate; screened couples having 
psychotic features; screened couples either having suicidal ideation or manic/hypomanic 
features; couples either having diabetes or cardiovascular disorders; any intellectual, visual, or 
hearing disability present in either spouse of a couple; history of miscarriage or infant mortality 
in one year; history or presence of diagnosis with psychiatric disorder and/or psychotropic 
medicine intake. 
 
Recruitment  
Recruitment will be carried by the investigator along with a research assistant after screening nth 
women along with their husbands coming for their routine check-ups at a clinic, Islamabad and 
Qamar Maternity hospital, Gujar Khan with Major Depressive Disorder Subscale and 
Generalized Anxiety Disorder Subscale of Parental Perinatal Distress Scale. Written informed 
consent will be sorted. Intervention arms of CBCT (conditions: with or without Zikr) will be 
carried out in Islamabad whereas rest of the arms will be carried out in Gujar Khan. It will not be 
a multisite randomization due to lack of resources and unavailability of funds.  
After going through the informed consent form, written consent was taken for participation in the 
study. A list of nth willing participants with preferred mode of treatment was prepared. The 
research assistant inquired the willing high-risk participants to select one of their preferred 
treatment modes out of the following: 
a. Medications (antidepressants and/or anxiolytics).  
b. Cognitive Behavioural Couple Therapy without Zikr.  
c. Cognitive Behavioural Couple Therapy with Zikr. 
d. Combination of medications and cognitive behavioral couple therapy without Zikr. 
e. Combination of medications, cognitive behavioral therapy, with Zikr.  
Randomization  
However, the participants will be allocated to treatment group or control by random number 
generation via online calculator [83] by a research assistant to maintain the principle of 
randomization. They were not provided with their preferred mode of treatment until completion 
of the study. They will be briefed in the follow-ups about the study and will be given preferred 
mode of treatment on approval. This information will be recorded in the investigator's files with 
a random number assigned. A research assistant will be allowed to look at these files after 
completion of the research. Consultant gynaecologist and a research assistant will look after the 
couples for their physical concerns during the study participation. Participants will receive 


11 
 
psychopharmacological treatment according to the National Institute for Health and Care 
Excellence guidelines [84] by a consultant gynaecologist.  
The couples in group 1 will be given medications or placebo for two weeks and/or for four 
weeks maximum by the consultant gynaecologist. In next two weeks, medication will be tapered 
off and eventually stopped. The couples in group 2 will be treated with ten CBCT sessions either 
with Zikr or without Zikr. The couples in group 3 will be provided with medication for two to 
four weeks and tapering off along with termination in two more weeks. They will also be 
provided with ten sessions of CBCT either with Zikr or without Zikr. The couples in group 4 will 
be given no intervention that is they carried out the routine gynaecological check-ups.  
Allocation, Allocation Concealment, and Double-Blind in Trial 
Allocation sequence in the list of nth participants was subjected to randomization [83]. 
Allocation concealment will be achieved by not letting the participants and research assistant 
know about the treatment or control arm.  The intervention mode will be sealed in an envelope 
with a random number.  A total of nth participants (Nth couples) were identified, screened and 
simple randomly allocated either to intervention group or control group by the research assistant 
[85, 86]. They will be assigned to parallel arms of either intervention (5 arms) or a control group 
by simple randomization through online calculator [83] with allocation ratio of 1:1 by the 
research assistant. The waitlist control group will be further divided into placebo receiving sub-
group and no intervention or routine gynecological checkup receiving sub-group. Both the 
participants and the research assistant will not know about the allocation identity of the couples 
either to the treatment or control group.  
The intervention group participants and waitlist control participants will be briefed about the 
study after completion and will be compensated with provision of their preferred mode of 
treatment. Thus, the participants and research assistant will be blinded to the nature of the 
treatment mode they will receive.  
Intervention   
After signed informed consent, the participants in CBCT (with or without Zikr) arm and 
combination of CBCT (with or without Zikr) with psychopharmacological arm will be provided 
with ten sessions (two sessions per week, each session 60 minutes of duration) in groups. The 
contents of all sessions (except session 4 and 5) for participants in condition with Zikr and 
without Zikr were same for 45 minutes. However, in the last 15 minutes of session 4 and 5, the 
participants with Zikr were imparted Zikr by the investigator whereas the participants without 


12 
 
Zikr carried out group discussion on philosophy of life, moderated by a research assistant. The 
contents of the sessions are briefly given as the following: 
In the first session, rapport will be build and pre-test assessment will be carried out. In the 
second session, participants will be psycho-educated for perinatal period distress, couples’ 
physical and mental health and impact on the fetus-infant, the prevalence of depression and 
anxiety, and the significance of identification. Progressive muscle relaxation exercises will be 
carried out along with deep breathing. Feedback on the session will be taken. In the third session, 
participants will be psycho-educated on the theoretical model of cognitive-behavioral couple 
therapy with some historical highlights and empirical standing. A thought log will be given for 
homework. Feedback for deep breathing and progressive muscle relaxation will be carried out. In 
the fourth, fifth, sixth, seventh, eighth, and ninth session, feedback will be taken on homework 
and session. Various techniques of Cognitive Behavioural Couple Therapy will be applied based 
on the nature and contents of identified precipitating, perpetuating, and present stressors. In 
addition, relevant techniques will be incorporated from other modalities with eclecticism. 
Tasbeeh in Zikr will be given to group 3 and group 5 who opted for it in the screening process. 
On the tenth visit, feedback on the session and homework will be taken. Post-test assessment will 
be done in the following two approaches Group 5 will be exposed to one of the two conditions.  
However, after the completion of the research, the intervention group and waitlist group (control) 
will be briefed and will be delivered with an intervention mode of treatment of their choice as 
selected earlier. 
Assessment Instruments 
 
In a qualitative approach, the semi-structured interview schedule will be used to explore the 
present stressors, their expectations, and perceptions about the effectivity of treatments for 
perinatal distress among couples at pre-test and post-test assessment. In quantitative approach, 
five reliable and valid instruments will be used. The levels of perinatal depression and perinatal 
anxiety will be measured by Major Depressive Disorder Subscale and Generalized Anxiety 
Disorder Subscale of Parental Perinatal Distress Scale (PPDS), comprised of 14 and 8 items, 
with Cronbach’s alpha reliability coefficients 0.89 and 0.82 respectively. The two subscales 
showed acceptable convergent, divergent, and discriminant validity. It is a Likert scale with “0” 
for “never” and “3” for “always” categories of response. The total scores for 22 items ranged 
from 0 to 66 with higher score indicating presence of high distress [87]. The levels of coping 
strategies will be measured by Urdu version [88] Dyadic Coping Inventory (DCI) comprised 37 
items with 1 to 5 scoring categories. However, items 36 and 37 will not be included in the 
scoring as these are evaluative items. Scores for the remaining 35 items range from 35 to 175. 


13 
 
The cut-off score below 111 showed below average dyadic coping, scores between 111-145 
showed normal dyadic coping range, score above 145 showed above average dyadic coping [89]. 
The levels of social support will be measured by Urdu version [90] Multidimensional Scale for 
Perceived Social Support (MSPSS) comprised 12 items with 1 to 7 scoring categories. Scores 
range from 12 to 84, with higher scores indicating higher levels of social support available for 
perinatal couples [91]. The levels of well-being will be measured by Urdu version [92] 
Flourishing Scale (FS) comprised 8 items with 1 to 7 scoring categories. Scores range from 8 to 
56, with higher scores indicating better wellbeing in perinatal couples [93]. The levels of 
perceived quality in physical (7 items), psychological (6 items), social (3 items), and 
environmental (8 items) aspects of life were measured by Urdu version [94] World Health 
Organization Quality of Life-BREF (WHOQOL-BREF) comprised 26 items with 1 to 5 scoring 
categories. Item 1 and item 2 were not included in the scoring domains because these were 
evaluative items. Scores for physical aspect of life ranged from 7 to 35, 6 to 30 for psychological 
aspect, 3 to 20 for social, and 8 to 40 for environmental aspect of life. The higher scores indicate 
better quality in that particular domain of life in perinatal couples. In manual transformation of 
these raw scores obtained with WHOQOL-BREF to 0-20 and 0-100 scale have been given [95]. 
However, the investigator will use raw scores obtained in four subscales separately as domain 
wise comparison is recommended in the manual.   
 
Discussion 
In Pakistan, scarce randomized controlled trials have been conducted to investigate perinatal 
depression and anxiety in women [62-64]. However, survey research with cross-sectional design 
have been conducted in rural and urban areas of Punjab, to examine the association among social 
support, quality of life, wellbeing, and coping strategies with depression and anxiety during 
antenatal and postnatal period. A study was conducted to explore the maternal depression in rural 
areas of North Punjab and empirical evidence showed high social support resulted in lower 
major depressive symptoms in women during postnatal period [96]. Similarly, another research 
study reported inverse significant correlation of antenatal depression with perceived quality of 
life in women [97]. Likewise, prenatal anxiety related with obsessions and compulsions 
predicted wellbeing negatively in pregnant women [98]. Poor coping strategies significantly 
predicted high antenatal depression and anxiety in pregnant women [99]. To fill in the gap, the 
present randomized clinical trial will investigate the impact of intervention on perceived quality 
of life, social support, wellbeing and coping skills of high risk couples with perinatal distress.  
The strength of the present study will be empirical exploration of impact of generic 
psychopharmacological intervention, CBCT (with or without Zikr), and combination of 


14 
 
psychopharmacology with CBCT (with or without Zikr) treatment in reducing perinatal distress 
(depression and anxiety) and improving perceived social support, wellbeing, quality of life, and 
coping strategies among the high risk screened couples for perinatal distress in Pakistan. The 
psychopharmacologic intervention will be used either with escitalopram, or sertraline, or 
alprazolam. The short-term use of the medications with preventive aim showed minor side-
effects that subside with passage of time. The inclusion criteria with dose restriction alprazolam 
(0.25 to 0.50 mg/day), or escitalopram (5 to 10 mg/day), or sertraline (12.5 to 25 mg/day) is in 
safety limits with no reported adverse events in mothers during perinatal period according to the 
experts [100-102]. However, the present study will record and report occurrence of side effects 
and adverse events (if any) with the use of psychopharmacological intervention in screened high 
risk couples for perinatal distress, provided with medication by a gynaecologist after evaluation 
of risk and benefits for preventive purposes.  
The current study is having certain limitations. Firstly, a complex research design (such as 
factorial, cross-over, cluster, multisite) in randomized clinical trial is not selected. Secondly, the 
sample size was small with 0.10 precision adjustments due to lack of financial resources and 
constraints of time duration for the completion of the present unfunded research project. Sample 
size with precision 0.05 must be increased in further experimental studies. A factorial design 
with main effect of escitalopram, sertraline, and alprazolam in a randomized controlled trial 
might be carried out to compare differential efficacy of drug used for reduction of the perinatal 
distress with screened high, medium, and low risk couples for preventive purposes.  A block 
design with or without Zikr bifurcation can be added to medication. Further, High Performance 
Liquid Chromatograph (HPLC) could be used to monitor safety and harmless impact of 
psychotropic drugs after stoppage. A randomized block design might be applied to segregate 
couples based on gender, age, and monthly income. A multisite cluster randomized trial could be 
designed by inclusion of either metropolitan cities or rural villages of Punjab.  
Conclusions  
The findings will imply for placement of psychologists/clinical psychologists in gynaecological 
wards of the hospitals and clinics for timely screening, prevention, and treatment the women and 
their husbands for mental health during perinatal period. Training workshops may be conducted 
for gynaecologists to sensitize them towards the issue of psychopathologies and their appropriate 
identification, screening, referral, and management in antenatal and postnatal period for better 
maternal and paternal wellbeing. 
 
 


15 
 
Acknowledgements 
Special thanks to Professor Ahmed Rafique Akhtar (Internationally Renowned Religious 
Scholar) and Quratulain Muhammad (MS, Clinical Psychologist). I am also grateful to Prof. Dr. 
Ghazala Mehmud, Professor and Head of Obstetrics and Gynaecology Fazaia Medical College 
and Air University Islamabad, Ex-Head Obstetrics-Gynaecology and Ex-Dean Pakistan Institute 
of Medical Sciences, Islamabad; Dr. Qamar-un-Nisa and Dr. Saroona Ishaq, Consultant 
Gynaecologists, Qamar Maternity Hospital, Gujar Khan. I am thankful to Dr. Fayyaz Ahmed 
(Associate Professor/Chairperson, Department of Statistics, University of Gujrat), Dr. 
Muhammad Zubair (Associate Professor, Department of Chemistry, University of Gujrat), and 
last but not least Mr. Zaheer Abbas (Lecturer, Department of Statistics, University of Gujrat) for 
their academic support and guidance. 
 
Duration of the Data Collection for RCT: 15th August, 2023 to 30th October, 2023. 
Phase 
Date  
Recruitment: 
Initial 
screening, 
selection, 
informed consent, and randomization 
15th August to August 26, 2023 
Session 1: Pre-test Assessment 
August 28, 2023 
Session 2 
August 31, 2023 
Session 3 
September 4, 2023 
Session 4 
September 7, 2023 
Session 5 
September 11, 2023 
Session 6 
September 14, 2023 
Session 7 
September 18, 2023 
Session 8 
September 21, 2023 
Session 9 
September 25, 2023 
Session 10: Post-test Assessment 
September 28, 2023 
1st follow-up 
October 14, 2023 
2nd follow-up 
October 28, 2023 
 
Author’s Contribution 
SS contributed to conceptualization, methodology, data acquisition, data analysis, draft writing 
and review as per ICMJE criteria of authorship.  
 
 
 


16 
 
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SAP_001.pdf: 
 
Statistical Analysis Plan 
Research Study 
Unique Protocol ID: UOG/ORIC/2022/393  
Brief Title: Cognitive Behavioral Couple Therapy for Perinatal Distress  
Official Title: The Effectiveness of Psychopharmacological Intervention Versus Cognitive 
Behavioural Couple Therapy and Their Combination in Perinatal Distressed Couples: A 
Randomized Clinical Trial 
Registration: NCT06001021 
Initial Registration: 26th June, 2023. 
Initial Approval and Public Release Date: 13th August, 2023. 
Statistical Analysis  
Mean difference for the impact of intervention across five intervention arms 
(psychopharmacological intervention; cognitive behavioural couple therapy; cognitive 
behavioural couple therapy along with Zikr; combined (Psychopharmacological Medication 
and Cognitive Behavioral Couple Therapy); combined (Psychopharmacological Medication 
and Cognitive Behavioral Couple Therapy along with Zikr), and two control arms (placebo 
comparator, and no intervention) is measured separately in the test scores for perinatal 
distress, dyadic coping, social support, wellbeing, and four domains of quality of life (i.e., 
physical, psychological, social, and environmental aspects) via ANCOVA after controlling 
for baseline pre-test scores for perinatal distress (depression and anxiety)  in SPSS-24.  
 
Mean difference for the impact of intervention across five intervention arms 
(psychopharmacological intervention; cognitive behavioural couple therapy; cognitive 
behavioural couple therapy along with Zikr; combined (Psychopharmacological Medication 
and Cognitive Behavioral Couple Therapy); combined (Psychopharmacological Medication 
and Cognitive Behavioral Couple Therapy along with Zikr), and two control arms (placebo 
comparator, and no intervention) is measured separately in the test scores for perinatal 
distress, dyadic coping, social support, wellbeing, and four domains of quality of life (i.e., 
physical, psychological, social, and environmental aspects) via ANCOVA after controlling 
for baseline pre-test scores for perinatal distress (depression and anxiety) and monthly 
income  covariates in SPSS-24.