Concurrent Psychotherapy Research Articles

Clinical case report: considerable improvement of severe and difficult-to-treat obsessive-compulsive disorder with comorbid depression under treatment with esketamine and concomitant psychotherapy

A 28-year-old man was admitted to our psychiatric ward with severe obsessive-compulsive disorder (OCD) and comorbid depression. At intake, obsessive-compulsive symptoms were present most time of the day and were related to an intense fear of causing interpersonal misunderstandings. Various treatment attempts, including cognitive-behavioural therapy (CBT) with exposure and response prevention (ERP), selective serotonin reuptake inhibitors, clomipramine, and add-on antipsychotics were either ineffective and/or were not tolerated, and the patient’s condition worsened progressively. Following an in-depth multidisciplinary team discussion and a shared decision-making process, an off-label treatment trial with esketamine and concomitant psychotherapy was started. The patient received 10 esketamine + psychotherapy sessions over a period of about 2 months, followed by two maintenance sessions in about 3-week intervals. After this, he was discharged into regular outpatient care where he continued to receive maintenance esketamine treatment every 4–6 weeks and, independent of this, individual CBT. Following the establishment of esketamine with concurrent psychotherapy, the patient exhibited a remarkable clinical improvement. Obsessive-compulsive symptoms showed a clear and sustained response (Y-BOCS before treatment >35, Y-BOCS at week 8 = 23, Y-BOCS at week 26 = 14). Paralleling this, depressive symptoms also decreased (MADRS before treatment = 47, MADRS at week 9 = 12, MADRS at week 26 = 3). At a naturalistic follow-up at week 66, obsessive-compulsive symptoms were still mild (Y-BOCS = 13), and depression was still in remission (MADRS < 6). This clinical case suggests that (es)ketamine plus concomitant psychotherapy may hold promise as a therapeutic strategy for difficult-to-treat OCD and depression and its full clinical potential should be evaluated in more comprehensive future studies.

A randomized controlled trial of surf and hike therapy for U.S. active duty service members with major depressive disorder

BackgroundMajor depressive disorder (MDD) is the most prevalent mental health disorder worldwide, including among U.S. service members. In addition to evidence-based treatments, activity-based approaches have been shown to effectively treat depressive symptoms, particularly when they occur in the natural environment.MethodsThis study compared two activity-based interventions, Surf Therapy and Hike Therapy, on depression outcomes among 96 active duty service members with MDD. Participants were randomized to 6 weeks of Surf or Hike Therapy. Clinician-administered and self-report measures were completed at preprogram, postprogram, and 3-month follow-up. A brief depression/anxiety measure was completed before and after each activity session.ResultsMultilevel modeling results showed that continuous depression outcomes changed significantly over time (ps < .001). Although service members in Hike Therapy reported higher average depression scores than those in Surf Therapy, the trajectory of symptom improvement did not significantly differ between groups. Regarding MDD diagnostic status, there were no significant differences between the groups at postprogram (p = .401), but Surf Therapy participants were more likely to remit from MDD than were those in Hike Therapy at the 3-month follow-up (p = .015).LimitationsThe sample consisted of service members, so results may not generalize to other populations. Most participants received concurrent psychotherapy or pharmacotherapy, and, although statistically accounted for, results should be interpreted in this context.ConclusionsBoth Surf and Hike Therapies appear to be effective adjunctive interventions for service members with MDD. Research is needed to examine the effectiveness of these therapies as standalone interventions.Trial registrationClinical trials registration numberNCT03302611; First registered on 05/10/2017.

Folie a trois: In mother and her twin adolescent daughters: Case report

Abstract Shared psychotic disorder is not uncommon and affects different sets of people with different profiles. Here we present a case of a mother and her two dizygotic daughters who showed suspiciousness and social withdrawal. The case is unique as even after hailing from a well-educated family, the social stigma and lack of awareness caused a surplus lapse in treatment. Close association, female gender, suggestibility, and untreated medical conditions in the primary can act as psychopathological factors. In such situations, separation along with concurrent pharmacotherapy and psychotherapy is advocated emphasizing individualized treatment.

A polygenic-informed approach to a predictive EEG signature empowers antidepressant treatment prediction: A proof-of-concept study

The treatment of major depressive disorder (MDD) is hampered by low chances of treatment response in each treatment step, which is partly due to a lack of firmly established outcome-predictive biomarkers. Here, we hypothesize that polygenic-informed EEG signatures may help predict antidepressant treatment response. Using a polygenic-informed electroencephalography (EEG) data-driven, data-reduction approach, we identify a brain network in a large cohort (N=1,123), and discover it is sex-specifically (male patients, N=617) associated with polygenic risk score (PRS) of antidepressant response. Subsequently, we demonstrate in three independent datasets the utility of the network in predicting response to antidepressant medication (male, N=232) as well as repetitive transcranial magnetic stimulation (rTMS) and concurrent psychotherapy (male, N=95). This network significantly improves a treatment response prediction model with age and baseline severity data (area under the curve, AUC=0.623 for medicaton; AUC=0.719 for rTMS). A predictive model for MDD patients, aimed at increasing the likelihood of being a responder to antidepressants or rTMS and concurrent psychotherapy based on only this network, yields a positive predictive value (PPV) of 69% for medication and 77% for rTMS. Finally, blinded out-of-sample validation of the network as predictor for psychotherapy response in another independent dataset (male, N=50) results in a within-subsample response rate of 50% (improvement of 56%). Overall, the findings provide a first proof-of-concept of a combined genetic and neurophysiological approach in the search for clinically-relevant biomarkers in psychiatric disorders, and should encourage researchers to incorporate genetic information, such as PRS, in their search for clinically relevant neuroimaging biomarkers.

Ketamine for Bipolar Depression: Biochemical, Psychotherapeutic, and Psychedelic Approaches.

Bipolar disorder (type 1) is a serious and chronic psychiatric illness that can be difficult to treat. Many bipolar patients have refractory depressive episodes. Racemic ketamine, a glutamate modulator with prominent dissociate and psychedelic properties, has been demonstrated to have rapid acting antidepressant and anti-obsessional effects which may be useful for treating the symptoms of bipolar depression. Most of the existing research literature on unipolar and bipolar depression has looked at racemic ketamine in the sub-psychedelic dose range given by infusion as a stand-alone treatment (without concurrent psychotherapy). This article expands on the existing research by articulating three different paradigms for ketamine treatment: biochemical, psychotherapeutic, and psychedelic. The authors use composite clinical vignettes to illustrate different ways of working with ketamine to treat bipolar depression, and discuss a variety of clinical considerations for using ketamine with this population, including route, dose, frequency, chemical mitigators, and adverse events. Note that the conceptual paradigms could be applied to any ketamine treatment, with broad applicability beyond bipolar treatment.

Repetitive Transcranial Magnetic Stimulation for Generalized Anxiety Disorder: A Systematic Literature Review and Meta-Analysis.

BackgroundAnxiety disorders such as generalized anxiety disorder (GAD) impact 10% of the US population, and many patients do not completely respond to first-line treatments (e.g., selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and psychotherapy). Given the dearth of evidence for non-pharmacologic, non-psychotherapeutic interventions, we performed a systematic review and meta-analysis of repetitive transcranial magnetic stimulation (rTMS) in adults with GAD.MethodsA systematic literature review using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted. Pre- and post-treatment anxiety scores were extracted, and a random-effects meta-analysis was conducted to determine the magnitude of improvement (standardized mean difference). Standard assessments of heterogeneity (e.g., Q-statistic, I2, and τ 2) and publication bias were performed.ResultsThe initial search resulted in 3194 citations, of which 6 studies were included in the meta-analysis. In total, 152 patients were studied, including 97 patients who received active treatment and 55 who received sham treatment, and heterogeneity was modest (I2 13.32, Q = 5.77). In patients with GAD, rTMS produced a standardized mean difference of −1.857 (confidence interval: −2.219 to −1.494; P < .001) with a prediction interval of −2.55 to −1.16.ConclusionsThe results suggest a robust effect of rTMS in GAD in the context of limited, heterogenous studies. Rigorously designed, randomized controlled trials of rTMS for GAD and related anxiety disorders are urgently needed. These studies will provide opportunities for biomarker development and integration of concurrent evidence-based psychotherapy to maximize results.

Psychiatric Profile and Response to Combined Pharmacologic and Psychotherapeutic Treatment in Psychogenic Purpura.

Objective: Psychogenic purpura is a rare psychocutaneous entity characterized by painful atraumatic, ecchymotic, and purpuric lesions that commonly occur in young women. The objective of this study is to describe the clinical presentation, psychiatric profile, and response to therapy (pharmacologic and psychotherapeutic) in patients with psychogenic purpura.Methods: Twenty-three patients, referred from various clinical departments with unexplained purpura or ecchymotic lesions, were assessed in the department of psychiatry of a tertiary care institute in eastern India over a period of 3 years (May 1, 2017, to April 30, 2020). Relevant systemic evaluation and routine biochemical and laboratory tests including complete blood count, bleeding time, clotting time, prothrombin time, coagulation profile, and platelet function test were conducted for all patients to rule out an underlying organic cause. Associated psychiatric comorbidities were diagnosed as per the International Classification of Diseases, 10th edition. All patients who were eventually diagnosed with psychogenic purpura received appropriate treatment (pharmacologic and psychotherapy) and were followed up for 1 year.Results: Seven female patients (age range, 14-70 years, mean age = 30.28 ± 17.42 years) were diagnosed with psychogenic purpura. All patients had significant stressors prior to the appearance of lesions. Facial involvement was reported in 2 patients (28.6%). Multiple sites were affected in 4 patients (57.1%). The underlying psychiatric conditions diagnosed were depressive disorder (42.9%), generalized anxiety disorder (28.6%), dissociative convulsion disorder (14.3%), and panic disorder (14.3%). Associated personality disorder was noted in 2 patients (28.6%). All patients were started on selective serotonin reuptake inhibitors and concurrent psychotherapy. A short course of benzodiazepine was used in all patients and was subsequently tapered off. At 1-year follow-up, 2 patients reported recurrences, while others continued to do well with no similar episodes.Conclusions: Appropriate psychiatric evaluation and necessary intervention in patients with psychogenic purpura lead to improved patient outcomes.

“We really need this”: Trauma-informed yoga for Veteran women with a history of military sexual trauma

ObjectivesUp to 70% of women service members in the United States report military sexual trauma (MST); many develop post-traumatic stress disorder (PTSD) and co-occurring disorders. Trauma-informed yoga (TIY) is suggested to improve psychiatric symptoms and shown feasible and acceptable in emerging research, yet no work has evaluated TIY in MST survivors. The current quality improvement project aimed to examine TIY’s feasibility, acceptability, and perceived effects in the context of MST. DesignCollective case series (N = 7). SettingNew England Vet Center. InterventionsExtant TIY program (Mindful Yoga Therapy) adapted for Veteran women with MST in concurrent psychotherapy. Main outcome measuresAttrition and attendance; qualitative exit interview; validated self-report measure of negative affect pre/post each yoga class, and symptom severity assessments and surveys before (T1; Time 1) and after the yoga program (T2; Time 2). ResultsFeasibility was demonstrated and women reported TIY was acceptable. In qualitative interviews, women reported improved symptom severity, diet, exercise, alcohol use, sleep, and pain; reduced medication use; and themes related to stress reduction, mindfulness, and self-compassion. Regarding quantitative change, results suggest acute reductions in negative affect following yoga sessions across participants, as well as improved affect dysregulation, shame, and mindfulness T1 to T2. ConclusionsTIY is both feasible and acceptable to Veteran women MST survivors in one specific Vet Center, with perceived behavioral health benefits. Results suggest TIY may target psychosocial mechanisms implicated in health behavior change (stress reduction, mindfulness, affect regulation, shame). Formal research should be conducted to confirm these QI project results.

3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for victims of sexual abuse with severe post-traumatic stress disorder: an open label pilot study in Brazil.

Objective:To conduct Brazil’s first clinical trial employing 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder (PTSD), given its high prevalence resulting from epidemic violence.Methods:Of 60 volunteers, four matched the inclusion & exclusion criteria. Three patients with PTSD secondary to sexual abuse (diagnosed by the Structured Clinical Interview for DSM-IV and the Clinician Administered PTSD Scale for DSMV-4 [CAPS 4]) completed enrollment and treatment, following a standardized Multidisciplinary Association for Psychedelic Studies protocol consisting of 15 weekly therapy sessions: three with orally administered MDMA with concurrent psychotherapy and music, spaced approximately 1 month apart. CAPS-4 scores two months after the final MDMA session were the primary outcome.Results:No serious adverse events occurred. The most frequent adverse events were somatic pains and anguish. CAPS-4 reductions were always greater than 25 points. The final scores were 61, 27, and 8, down from baseline scores of 90, 78, and 72, respectively. All reductions were greater than 30%, which is indicative of clinically significant improvement. Secondary outcomes included lower Beck Depressive Inventory scores and higher Post-Traumatic Growth Inventory and Global Assessment of Functioning scores.Conclusion:Considering the current limitations in safe and efficacious treatments for PTSD and recent studies abroad with larger patient samples, MDMA-assisted psychotherapy could become a viable treatment in Brazil.Clinical trial registration:RBR-6sq4c9

A retrospective chart review to determine the safety and efficacy of prazosin for nightmares related to posttraumatic stress disorder in veterans.

To evaluate the efficacy of prazosin for posttraumatic stress disorder (PTSD)-related nightmares in veterans and to analyze subgroup benefit/risk to guide prescribing. Patients with a previous prescription for prazosin between 1 June 2007 and 30 June 2017 were collected from the institution's electronic records. Efficacy (including nightmare frequency, and clinical PTSD rating scales) and safety (including blood pressure) data were retrospectively analyzed. Eighty-four patients were included in the analysis. The primary outcome, item 2 of the PTSD checklist, decreased from 4.00 to 3.19 (on a scale of 1-5), which was statistically significant (p<0.05). Nightmare frequency was found to have a statistically significant decrease from four to two times per week on average (p=0.00002, 95% CI 2.36 [1.39-3.33]). Of the patients who reported the greatest response (n=23), 91% (n=21) were on an antidepressant and 61% (n=14) were receiving concurrent psychotherapy. This is compared to 90% (n=76) and 44% (n=37) of the total cohort, respectively. No significant differences were found in blood pressure or suicidal ideation (p=0.58 and p=0.22, respectively). Prazosin may be considered as an adjunct option to decrease nightmare frequency in patients already receiving first-line treatment.

Trauma-focused psychodynamic therapy and STAIR Narrative Therapy of post-traumatic stress disorder related to childhood maltreatment: trial protocol of a multicentre randomised controlled trial assessing psychological, neurobiological and health economic outcomes (ENHANCE)

IntroductionSuccess rates of psychotherapy in post-traumatic stress disorder related to childhood maltreatment (PTSD-CM) are limited.Methods and analysisObserver-blind multicentre randomised clinical trial (A-1) of 4-year duration comparing enhanced methods of STAIR...

Combined and parallel individual and group therapy—still a red rag?

The author argues that in specific cases, and for particular reasons, combined or parallel treatment could be superior to sole individual or sole group therapy. In recent years, I treated some patients before and during the start of group therapy with weekly individual sessions. This procedure was necessary to reduce the fear of the group for these patients to a tolerable level. For some other patients, I replaced the third psychoanalytic individual session with psychoanalytic group therapy for their treatment. The concurrent parallel group session can provide a supplement and extension of the psychoanalytic process. For patients with pronounced super-ego disorders, severe shame and social anxieties, this treatment may boost individual development in treatment. Concurrent group and individual psychotherapy enriches transference and countertransference work in both settings and enables a dense and intensive therapeutic process. To treat people equally means to treat them differently. The needs of our patients are not the same. The main point of my interest is the patient and not the treatment modality. Every patient requires individual ways of therapy.

Family‐Based Recovery: An Innovative Collaboration between Community Mental Health Agencies and Child Protective Services to Treat Families Impacted by Parental Substance Use

To meet the needs of families who have very young children and are involved with child protective services due to substance use, the State of Connecticut Department of Children and Families, Yale Child Study Center and Johns Hopkins University created an innovative treatment model. This public–private collaboration required a paradigm shift for both child protective services staff and treatment providers. This brief description of the Family‐Based Recovery model highlights the family‐focused practice elements that allow children to remain safely at home with parents who are in treatment. Outcomes suggest that Family‐Based Recovery is a promising practice, and collaborations between child protective services and substance use treatment providers can yield positive results for families with young children.‘Highlights the family‐focused practice elements that allow children to remain safely at home with parents who are in treatment’Key Practitioner Messages Strong collaboration between child protective services and treatment providers can mitigate the risk of out‐of‐home placement for children impacted by parental substance use. In‐home treatment that provides concurrent psychotherapy, substance use treatment and parent–child dyadic therapy is an important part of the service array for families involved with child protective services.

Impact of a clinical pharmacist-managed clinic in primary care mental health integration at a Veterans Affairs health system.

Introduction:The demand for mental health (MH) services has increased as more veterans seek MH care. At the South Texas Veterans Health Care System, Primary Care Mental Health Integration (PCMHI) was developed to manage patients with uncomplicated MH conditions, including depression, anxiety, or posttraumatic stress disorder (PTSD), within an interdisciplinary primary care (PC) team that includes clinical pharmacy specialists (CPSs). Pharmacists have improved outcomes and access to care for many chronic medical conditions, but limited data demonstrate the impact of MH pharmacists within PC.Methods:This project evaluated the impact of a PCMHI CPS clinic on managing patients with recent antidepressant initiation and CPS clinic intake from September 2015 through December 2016, including follow-up through January 2017. Markers used to evaluate effectiveness of the service included the Patient Health Questionnaire-9 scores, antidepressant medication possession ratio, number of emergency department visits for MH-related concerns, patient engagement in concurrent psychotherapy, and referrals to specialty MH providers.Results:A total of 196 unique patients had intake with the PCMHI CPS in the time specified; 172 of these patients were included in analyses. There were 155 patients maintained in PC. Average Patient Health Questionnaire-9 scores decreased from 14.5 to 8.5, with 63 patients (46%) achieving response and 42 patients (31%) achieving remission. The average antidepressant medication possession ratio was 0.93 for all included patients.Discussion:A PCMHI CPS successfully manages and maintains patients with uncomplicated MH conditions in PC through evidence-based pharmacotherapy, as evidenced by symptom improvement, medication adherence, and low rate of specialty MH referrals.

The Balancing Act: Concurrent Parent-Child Work

ABSTRACTThis article examines some of the challenges of parent work and the historical roots for why parent work has assumed a more marginal role in the treatment of children. The author contends that parent work is critical in the overall structure of a child’s treatment. The article describes concurrent parent psychotherapy, a psychoanalytically informed approach developed by Jack and Kerry Novick that emphasizes dual goals, two systems of self-regulation, and a framework for building and maintaining multiple therapeutic alliances. These principles are illustrated with a discussion of concurrent work with parents and their young son, who was prone to explosive behavior in school. Addressing parenthood as a developmental phase, the article covers typical anxieties parents bring to treatment and shows how the ongoing involvement of the boy’s parents helped him develop and consolidate inner controls and a more benign superego.

Antidepressant Use by Youth with Minimal or Mild Depression: Evidence from 3 Health Systems.

Background:There is concern about the prevalence of prescribing antidepressant medications to youth without appropriate diagnoses or who have subthreshold (mild) depression.Methods:Electronic records data from 3 large healthcare systems identified youth aged ≤21 years starting a new episode of antidepressant treatment between January 1, 2009, and December 31, 2013. For those with a diagnosis of depression, Patient Health Questionnaire (PHQ9) scores at the time of treatment initiation were used to examine the distribution of symptom severity and patients' demographic and clinical characteristics.Results:Of the 15,460 episodes of treatment, a depression diagnosis was recorded in 95% of the cases. PHQ9 scores were available for 4,329 youth with a diagnosis of depression. Younger age, sex, previous treatment, co-occurring anxiety, treatment setting, concurrent psychotherapy, and site were significant predictors of completing a PHQ9. Among youth with a baseline score, 87% reported moderate or severe symptoms (PHQ9 score ≥ 10) and 13% reported mild or minimal symptoms (PHQ9 < 10). The proportion reporting PHQ9 < 10 when starting treatment decreased with age, ranging from 19% in those aged 13–14 years and 12% in those aged 18–21 years. Patients treated by psychiatrists were 1.54 times (95% Confidence Interval [CI], 1.21–1.97) more likely to have PHQ9 scores < 10 compared with primary care physicians. Patients with prior treatment history (odds ratio = 1.76; 95% CI, 1.45–2.13) and concurrent psychotherapy (odds ratio = 1.24; 95% CI, 1.02–1.52) were more likely to have PHQ9 < 10.Conclusions:In these health systems, prescribing of antidepressant medication to adolescents for minimal or mild depression is much less common than previous reported.

Frontline clinicians’ perspectives on and utilization of trauma-focused therapy with individuals with eating disorders

ABSTRACTWith this study, we sought to survey clinicians regarding their perspectives and use of concurrent or integrated psychotherapy for co-occurring eating disorders (EDs) and posttraumatic stress disorder. We conducted a quantitative survey of 184 frontline ED clinicians to investigate whether, and to what extent, they view concurrent EDs and trauma-focused therapy as clinically important. We also assessed clinicians’ specific concerns regarding concurrent EDs and trauma-focused treatment, as well as barriers to implementation of an evidence-based concurrent treatment. On the whole, clinicians reported that addressing trauma-related symptoms in individuals with EDs is highly important and should be administered concurrently. Although clinicians reported anticipating many important benefits of concurrent treatment, they also reported anticipating several potential negative side effects, and they reported a number of perceived barriers to implementation. Clinicians working in hospital settings anticipated more complications, expected fewer benefits, and perceived more barriers to the administration of concurrent treatment.

A meta-analysis of topiramate's effects for individuals with alcohol use disorders.

Influenced by several trials and reviews highlighting positive outcomes, topiramate is increasingly prescribed as a treatment for alcohol use disorders (AUDs). The only previously published meta-analysis of topiramate for AUDs was limited by a sample of only 3 randomized, placebo-controlled trials (RCTs). A systematic search identified 7 RCTs (including a total of 1,125 participants) that compared topiramate to placebo for the treatment for AUDs. This meta-analysis estimated the overall effects of topiramate on abstinence, heavy drinking, craving, and γ-glutamyltranspeptidase (GGT) outcomes and included several sensitivity analyses to account for the small sample of studies. Overall, the small to moderate effects favored topiramate, although the effect on craving was not quite significantly different from 0. The largest effect was found on abstinence (g = 0.468, p < 0.01), followed by heavy drinking (g = 0.406, p < 0.01), GGT (g = 0.324, p = 0.02), and craving (g = 0.312, p = 0.07) outcomes. Sensitivity analyses did not change the magnitude or direction of the results, and tests did not indicate significant publication bias. The small sample size did not allow for examination of specific moderators of the effects of topiramate. Topiramate can be a useful tool in the treatment of AUDs. Its efficacy, based on the current sample of studies, seems to be of somewhat greater magnitude than that of the most commonly prescribed medications for AUDs (naltrexone and acamprosate). Further research will help to identify the contexts in which topiramate is most beneficial (e.g., dose, concurrent psychotherapy, patient characteristics).

Concurrent group psychotherapy for transgenerationally traumatized school age children and their parents in a transcultural context

Concurrent group psychotherapy for transgenerationally traumatized school age children and their parents in a transcultural context

Utilization of 5HTT-gene polymorphism as a prognostic indicator in cancer.

TPS139 Background: Clinical studies show an association between depression and cancer outcomes as decreased desire for life- sustaining treatment and increased mortality. Neurotransmitters are capable of altering immune function whereas immune-derived mediators regulate neuroendocrine and autonomic outflow from the brain. Host cellular defenses against cancer involve immune-mediated mechanisms that can be influenced by neurotransmitter activity. Recent studies on polymorphism of the 5-HTT gene explain why some individuals develop psychological morbidities on exposure to stressful life events while others exposed to the same conditions do not. This offers a screening criterion for identifying patients at risk for psychological morbidity that might be detrimental to their treatment outcome and may be used as a prognostic indicator in which case, starting anticancer treatment of this group of patients with concurrent psychological intervention may improve their treatment outcomes. Aim: To study the role of 5HTT gene as a prognostic indicator in cancer and its utilization for clinical selection of patients for concurrent psychotherapy with anticancer treatment. Methods: A simultaneous two study program. Study I: a longitudinal observational study in which cancer outcomes are compared in two independent cohorts of cancer patients grouped by 5HTT genotype (patients with two long alleles versus those with at least one short allele). In Study II, patients with at least one short allele will be randomized into either an intervention arm receiving anticancer treatment accompanied by supportive psychiatric care program or control arm receiving standard care (anticancer treatment without psychotherapy). Outcomes: Primary outcome is progression-free survival. Secondary outcomes are response to treatment, functional and psychological status of the patient as expressed by Quality of Life measurement using FACT-G questionnaire and the Hospital Anxiety and Depression Scale, and overall survival. No significant financial relationships to disclose.