Evaluation of a Male-specific Psychotherapeutic Program for Major Depressive Disorders

Study Overview
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Brief Summary
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This project aims to evaluate a male-specific psychotherapeutic program (MSPP) for MDD based on cognitive behavioral therapy (CBT). The primary goal is to test the superiority of the MSPP. This will be conducted in two groups of depressed men, namely eudonadal depressed men and hypogonadal depressed men receiving testosterone treatment (TT). In a randomized study design, the MSPP will be compared to a standard CBT and a waitlist control group, resulting in a total of six study groups. Both standardized psychotherapy programs will encompass 18 sessions delivered in a weekly manner, starting at study week 6 and continuing until study week 24. Aligned with the TT-related medical visits of the hypogonadal men, all participants will be followed up with clinical assessments and biosampling at weeks 0, 6, 15, 24, 36. In addition, a separate healthy control group will be examined, which will undergo only baseline assessments.

Detailed Description
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Background: Although women are twice as likely to suffer from major depressive disorder (MDD) than men, there are still over 100 million men affected by this condition worldwide. Unfortunately, men suffering from MDD seek mental health services about 30% less than women, leaving a large portion of men with unresolved mental health needs. This is reflected in 2-fold higher rates of alcohol use disorder and 4-fold higher rates of completed suicide amongst men, while MDD is considered a prime risk factor for both. A case is made for male-typical MDD phenotypes with differing symptom presentation often unrecognized by clinicians. Although cognitive behavioral therapy (CBT) represents an effective treatment for MDD, conformity to traditional masculinity norms based on stoicism, self-reliance, and restrictive emotionality often hinder men from engaging in psychotherapy. Therefore, a need to address this diagnostic and treatment gap emerges, while recent studies have identified a lack of male-specific psychotherapeutic programs (MSPP) that could persuade more men to take on psychotherapy based on a male-tailored nature, focusing on male-specific topics and being introduced in male-typical environments. Method and study procedures: In total, 144 depressed men aged between 25 and 50 will be recruited. After Screening procedures, included participants are stratified by testosterone status (hypogoadal vs. eugonadal) and randomized to one of the conditions: MSPP, CBT, Waitlist. This results in six intervention groups (MSPP, CBT, Waitlist, MSPP+TT, CBT+TT, Waitlist+TT). Hypogonadal men will receive testosterone treatment administered at the Andrology-Urology Center (Uroviva). MSPP and CBT intervention groups will receive weekly therapy sessions for MDD over 18 weeks. All participants will be invited to a total of five examination appointments (weeks 0, 6, 15, 24, 36) at the psychological institute of the university of Zurich. In addition, a separate healthy control group will be examined, which will undergo only baseline assessments. Expected results: Compared to the waitlist control groups, the treatment groups are expected to be more effective and efficacious (depression score reduction of ≥50%) at week 24 and at follow-up week 36. The MSPP, compared to CBT, is expected to show higher effectiveness and efficacy for depression symptoms, higher acceptability and a greater reduction of gender role conflict. In addition, it is expected that the initially hypogonadal men will have increased symptom improvement due to TT as compared to the eugonadal men in the parallel groups and that TT receiving men show an adjunct effect of added psychotherapy as compared to men in the waitlist.

Official Title
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Evaluation of a Male-specific Psychotherapeutic Program for Major Depressive Disorders Compared to Standard Cognitive Behavioral Therapy: A Randomized Controlled Superiority Trial

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Behavioral: Male-specific psychotherapeutic program (MSPP)
* Behavioral: Cognitive beahvioral therapy (CBT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male sex Age between 25 - 50 years German speaking Current major depression (assessed by SCID-5) Informed consent as documented by signature Exclusion Criteria: Inability to give informed consent Prior hormonal (testosterone) treatment Prior mental health disorder Current or previous psychopharmacological treatment Current or previous psychological treatment for any psychological disorder - Exception for persistent depressive disorder (Dysthymia) and alcohol/substance use disorder of mild degree (SCID-5, 1 - 3 criteria met) Comorbidities of major depression with any other psychological disorder Severe physical disorder that requires priority treatment Any of the following physical conditions, particularly relevant in regard to testosterone treatment: Diagnosed prostate cancer Prostatic intraepithelial neoplasia (PIN) Severe lower urinary tract symptoms Erythrocytosis Sleep apnea, diagnosed but untreated Current treatment with: Thyroid hormones Finasteride Antiepileptic drugs Anabolic compounds Hypnotic medication more than 2 nights/week for the treatment of insomnia Long-acting benzodiazepines Antipsychotic medication Drugs that affect serum testosterone Genetic / hormonal disorders: Klinefelter's syndrome Cushing's disease Addison's disease Hashimoto Thyroiditis

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: six-arm randomized controlled superiority trial 2x3 factorial study design Additionally, a healthy control group will be examined, which will undergo only baseline assessments. The study is a six-arm randomized controlled superiority trial. Participants will be stratified by testosterone status (eugonadal / hypogonadal) and then randomized into one of the three groups (MSPP, CBT or Waitlist). The study presents a 2x3 factorial study design. In addition, a separate healthy control group will be examined, which will undergo only baseline assessments.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: male-specific psychotherapeutic program (MSPP)<br>In this treatment group, eugonadal depressed men will receive the male-specific adjusted psychotherapy for depressive disorders (MSPP) based on cognitive behavioral principles in a single setting. | Behavioral: Male-specific psychotherapeutic program (MSPP)<br>* The MSPP for MDD is designed to be used for the acute treatment of depression in men in 18 sessions over a period of 18 weeks. Therapy is delivered weekly with homework bridging every session. Central CBT elements (e.g. behavioral activation, cognitive restructuring) will be retained in MSPP. During implementation of typical CBT techniques, masculine role norms will be considered. One underlying topic will be the potential of multiple masculinities to coexist, being fluid and relational within one man, emphasizing positive aspects of masculinities compatible with psychotherapy for MDD.<br>|
| Active Comparator: cognitive behavioral therapy (CBT)<br>In this treatment group, depressed men will receive standard cognitive behavioral psychotherapy for depressive disorders (CBT) in a single setting. | Behavioral: Cognitive beahvioral therapy (CBT)<br>* This intervention consists of 18 sessions of manualized, standard cognitive behavioral therapy for major depression. Therapy is delivered weekly with homework bridging every session.<br>|
| No Intervention: Waitlist<br>The participants in the Waitlist group are required to complete a waiting period of 36 weeks prior receiving the MSPP. As an additional safety measure, participants will be monitored by means of three appointments at week 6, 10 and 14 with a study psychologist. Subsequently, monthly telephone calls at week 18, 22, 26, and 30 are conducted. During these appointments no intervention will occur, while a treatment relationship is to be established so that the patient can describe his specific life circumstances and report possible symptom exacerbations or suicidality. | |
| Experimental: male-specific psychotherapeutic program (MSPP) + testosterone treatment (TT)<br>In this treatment group, hypogonadal depressed men will receive the male-specific adjusted psychotherapy for depressive disorders (MSPP) based on cognitive behavioral principles in a single setting. Further participants receive a standard testosterone replacement therapy consisting of testosterone undecanoate administered via deep intramuscular injection. | Behavioral: Male-specific psychotherapeutic program (MSPP)<br>* The MSPP for MDD is designed to be used for the acute treatment of depression in men in 18 sessions over a period of 18 weeks. Therapy is delivered weekly with homework bridging every session. Central CBT elements (e.g. behavioral activation, cognitive restructuring) will be retained in MSPP. During implementation of typical CBT techniques, masculine role norms will be considered. One underlying topic will be the potential of multiple masculinities to coexist, being fluid and relational within one man, emphasizing positive aspects of masculinities compatible with psychotherapy for MDD.<br>|
| Active Comparator: cognitive behavioral therapy (CBT) + testosterone treatment (TT)<br>In this treatment group, hypogonadal depressed men (blood testosterone ≤ 12.1 nmol/l) will receive standard cognitive behavioral psychotherapy for depressive disorders (CBT) in a single setting. Further participants receive a standard testosterone replacement therapy consisting of testosterone undecanoate administered via deep intramuscular injection. | Behavioral: Cognitive beahvioral therapy (CBT)<br>* This intervention consists of 18 sessions of manualized, standard cognitive behavioral therapy for major depression. Therapy is delivered weekly with homework bridging every session.<br>|
| No Intervention: Waitlist + testosterone treatment (TT)<br>The participants in the Waitlist group are required to complete a waiting period of 36 weeks prior receiving the MSPP. As an additional safety measure, participants will be monitored by means of three appointments at week 6, 10 and 14 with a study psychologist. Subsequently, monthly telephone calls at week 18, 22, 26, and 30 are conducted. During these appointments no intervention will occur, while a treatment relationship is to be established so that the patient can describe his specific life circumstances and report possible symptom exacerbations or suicidality. Further participants receive a standard testosterone replacement therapy consisting of testosterone undecanoate administered via deep intramuscular injection. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline observer assessed depressive symptomatology to post treatment | Observer assessed depressive symptomatology measured with the Hamilton Depression Rating Scale (HDRS-21) | baseline / 24 weeks | 
| Changes in the clinical symptomatology from baseline to post treatment | Observer assessed clinical symptomatology measured with the Clinical Global impression Scale (CGI-S/I) | baseline / 24 weeks | 
| Change from baseline male typical depressive symptomatology to post treatment | Self-reported male typical depression symptoms including externalizing behavior such as aggression, risk taking, or alcohol consumption measured with the Male Depression Risk Scale (MDRS-22) | baseline / 24 weeks | 
| Change from baseline self-reported depressive symptomatology to post treatment | self-reported depressive symptomatology measured with the Beck Depression Inventory (BDI-II) | baseline / 24 weeks | 
| Changes in gender role conflict | Self-reported symptoms of gender role conflict measured with the Gender Role Conflict Scale (GRCS-16) | baseline / 24 weeks | 
| Drop out | Acceptability: Proportion of men who withdraw for any reason (dropout) will be recorded and if dropped out participants consent, a dropout interview will be conducted to examine the reasons for dropout. | at follow up week 36 | 
| Achieved remission | Proportion of participants, that achieved depressive symptom remission (assessed by structured clinical interview [SCID-5-CV] for DSM-V disorders) | post treatment week 24 | 
| Changes in the therapeutic alliance quality | Self reported working alliance quality with the therapist | week 6 / week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skala Suizidales Erleben und Verhalten (SSEV-9) | Self-reported suicidal experience and behavior | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| Suicide Cognitions Scales (SCS-18) | Self-reported attitudes toward suicide | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| Problematic Pornography Consumption Scale (PPCS-18) | Self-reported pornography use and problematic consumption | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| Alcohol Use Disorder Test 10 (AUDIT-10) | Self-reported alcohol consumption symptomatology | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| International Index of Erectile Function 15 (IIEF-15) | Self-reported sexual dysfunction and libido symptomatology | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| Perceived Stress Scale (PSS-10) | Self-reported subjective stress | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| Generalized Anxiety Disorder (GAD-7) | Self-reported general anxiety | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| Conformity Masculine Norms Inventory (CMNI-30) | Self-reported conformity to traditional male role norms | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| Male Role Norms Inventory - Short Form (MRNI-SF-21) | Self-reported socially learned male role norms | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| Precarious Manhood Beliefs Scale (PMB-4) | Self-reported precarious manhood beliefs | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| Loneliness Scale (LS-20) | Self-reported feeling of loneliness and social isolation | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| Self-Compassion Scale D (SCS-D 10) | Self-reported Positive attitude towards oneself in difficult life situations | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| Emotion Regulation Questionnaire (ERQ-10) | Self-reported tendency to re-evaluate / suppress emotions | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| General Belongingness Scale (GBS) | Self-reported achieved belongingness | baseline / week 6 / week 15 / post treatment week 24 / follow up week 36 | 
| CIDI-Traumaliste (CIDI-T-12) | Assessment of self-reported traumatic experiences over the life span | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| International Trauma Questionnaire (ITQ-18) | Self-reported core symptoms of post-traumatic stress disorder and complex post-traumatic stress disorder | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| Agression Questionnaire Buss and Perry (AQ-BP) | Self-reported anger and aggression symptomatology | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| Fragebogens zum Körperbild (FKB-6) | Self-reported attitudes towards one's own and an ideal body image | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| Male Body Attitudes Scale-Revised (MBAS-R-15) | Self-reported male-specific body (dis)satisfaction | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| Body Appreciation Scale 2 (BAS-2-10) | Self-reported assessment of a positive body image | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| Stigma questionnaire (STIG-9) | Self-reported experienced stigma for suffering from a mental illness | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| Self-stigma of seeking psychological help (SSOSH-10) | Self-reported experienced stigma of seeking help | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| SHAME Questionnaire (SHAME-21) | Self-reported physical, cognitive and existential shame | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| Test of Self-Conscious Affect (TOSCA-16) | Assessment of susceptibility to guilt, shame, externalization, and unconcern (self-report questionnaire). | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| Toronto Alexithymia Scale (TAS-20) | Self-reported difficulty identifying and describing emotions | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| Multidimensional Self-Concept Scale (MSCS) | Self-reported self-concept (self-worth) | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| Arnett Inventory of Sensation Seeking (AISS-20) | Self-reported seeking of intense experiences including risky behavior | baseline / week 6 / post treatment week 24 / follow up week 36 | 
| Need to Belong Scale (NTBS-10) | Self-reported motivation to be accepted by others and avoidance of rejection by others | baseline / week 6 / post treatment week 24 / follow up week 36 |