Pharmacogenomic Characterization of Childbearing-Aged Individuals With Mood Disorders in a Tertiary Care Perinatal Mental Health Clinic.

Objective: The effectiveness of antidepressant treatment for mood disorders is often limited by either a poor response or the emergence of adverse effects. These complications often necessitate multiple drug trials. This clinical challenge intensifies during pregnancy, when medications must be selected to improve the likelihood of response and optimize reproductive outcomes. We determined the distribution of common pharmacogenetic variants, metabolizer phenotypes, past medication responses, and side effects in childbearing-aged individuals seeking treatment in a tertiary care perinatal mental health clinic.Methods: Sixty treatment-seeking women (based on sex at birth) with DSM-5- defined bipolar disorder (n = 28) or major depressive disorder (n = 32) provided DNA samples and completed psychiatric diagnostic and severity assessments between April 2014 and December 2017. Samples were genotyped for single-nucleotide variants in drug metabolizing enzyme genes of commonly prescribed antidepressants (cytochrome P450 [CYP] 1A2, 2B6, 2C9, 2C19, 2D6, 3A4, and 3A5), and the frequency of normative metabolizer status was compared to reference populations data from Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The Antidepressant Treatment History Form was used to record historic medication trials and side effects.Results: A significantly greater proportion of extensive metabolizers for CYP2B6 was observed in the study population when compared to CPIC population frequency databases in Caucasians (0.64 vs 0.43 [95% CI: 0.49-0.76]; P value = .006) and African Americans (0.71 vs 0.33 [95% CI: 0.29-0.96]; P value = .045). No significant association was found between metabolizer phenotype and the likelihood of a medication side effect.Conclusion: Pharmacogenomic testing may have value for personalized prescribing in individuals capable of or considering pregnancy.

Sex differences in effectiveness and adverse effects of mood stabilizers and antipsychotics: A systematic review.

BACKGROUND: Psychiatric disorders differ in their prevalence, symptom profiles, and disease courses in men and women. However, sex differences in psychiatric disorders have not received enough attention to guide treatment recommendations. This systematic review aims to summarize sex differences in the treatment responses and adverse effects of mood stabilizers and antipsychotics transdiagnostically. METHODS: We conducted a systematic review following the PRISMA 2020 statement (CRD42020212478). A literature search was conducted using MEDLINE, Embase, Cochrane Central, PsycINFO, Web of Science Core Collection, and Scopus databases. Studies comparing mood stabilizer or antipsychotic treatment outcomes in men and women were included. JBI critical appraisal checklists were used to assess bias risk. RESULTS: Out of 4866 records, 129 reports (14 on mood stabilizers, 115 on antipsychotics) with varying designs were included. Sample sizes ranged from 17 to 22,774 participants (median = 147). The most common psychiatric diagnoses were schizophrenia spectrum (n = 109, 84.5 %) and bipolar disorders (n = 38, 29.5 %). Only four studies explored sex differences in mood stabilizer treatment response. In 40 articles on antipsychotic treatment response, 18 indicated no sex difference, while 16 showed females had better outcomes. Women had more adverse effects with both mood stabilizers and antipsychotics. The risk of bias was low in 84 (65.1 %) of studies. LIMITATIONS: Substantial heterogeneity among the studies precluded performing a meta-analysis. CONCLUSION: Number of studies focusing on sex differences in treatment outcomes of mood stabilizers is limited. Women may respond better to antipsychotics than men, but also experience more side effects. The impact of pharmacokinetics on sex differences warrants more attention.

Pharmacogenomic overlap between antidepressant treatment response in major depression & antidepressant associated treatment emergent mania in bipolar disorder.

There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania.

The impact of fetal surgical procedures on perinatal anxiety and depression.

BACKGROUND: Perinatal mental illness presents a significant health burden to both patients and families. Many factors are hypothesized to increase the incidence of perinatal depression and anxiety in the fetal surgical population, including uncertain fetal prognosis and inherent risks of surgery and preterm delivery. OBJECTIVE: This study aimed to determine the incidence and disease course of postpartum depression and anxiety in the fetal surgery population. STUDY DESIGN: A retrospective medical record review study was conducted of fetal surgery patients delivering between November 2016 and November 2021 at an academic level IV perinatal healthcare center. Demographics and surgical, obstetrical, and psychiatric diagnoses were abstracted. Standard descriptive analyses were performed. RESULTS: Eligible patients were identified (N=119). Fetal surgery was performed at a mean gestational age of 22.8 weeks (standard deviation, 4.11). Laser ablation of placental anastomoses (n=51) and in utero myelomeningocele repair (n=22) were the most common procedures. Of 119 patients, 34 (28.6%) were diagnosed with preexisting depression or anxiety, with 19 (55.9%) and 17 (50.0%) on baseline medication for depression or anxiety, respectively, before surgery. Of 85 patients, 23 (27.1%) without a history of anxiety or depression had new identification of one or both after delivery. Of note, 2 patients experienced suicidal ideation after delivery. Of the 119 patients, 8 (6.7%) and 12 (10.1%) initiated a new psychiatric medication during or after pregnancy, respectively, and 19 (16.0%) received a therapy referral. Among patients with baseline anxiety or depression, 20 of 34 patients (58.8%) experienced an exacerbation after delivery, 9 of 34 patients (26.5%) were referred for therapy, 9 of 34 patients (26.5%) were changing dose or medication for anxiety, and 11 of 34 patients (32.4%) were changing dose or medication for depression. Of the 119 patients, 24 (20.2%) experienced new or worsening depression or anxiety after the standard 6-week postpartum visit. CONCLUSION: Among patients undergoing fetal surgery, a high incidence of postpartum depression and anxiety was identified, with most patients with prepregnancy anxiety or depression experiencing exacerbation after delivery. The timeframe to clinical presentation with depression or anxiety symptoms may be delayed beyond the traditional 6-week postpartum period and into the first postpartum year. This observation could be attributed to de novo postpartum exacerbation or a lack of standardized treatment approaches earlier in the disease course or antepartum period. Understanding effective longitudinal supportive interventions is an essential next step.

Assessing psychiatric risk with a focus on optimizing patient satisfaction with penile prosthesis placement-a narrative review.

Background and Objective: Treatment for medication-refractory erectile dysfunction (ED) is based on a shared decision-making model. The gold standard treatment for medication refractory ED is penile prosthesis (PP) placement. Patient satisfaction rates with PP are high with adequate counseling and expectation-setting. However, as with any elective surgery, patient selection is key to minimizing complications and ultimately patient dissatisfaction. Psychological well-being is an important consideration in the preoperative evaluation and postoperative management of patients undergoing PP placement. Methods: We performed a PubMed literature review to identify pertinent studies for this narrative review. Specifically, we sought describe preoperative evaluation including appropriate counseling and patient selection as well relevant intraoperative and postoperative factors for patients undergoing PP placement with a specific focus on optimizing preoperative psychiatric factors and treatment-related patient satisfaction to identify pertinent articles describing ways to optimize patient satisfaction with PP. Key Content and Findings: A patient's psychological state can influence the degree of understanding of their condition, affect perception of their treatment team, and limit their ability to cope with complications. All patients should undergo a thorough medical history and physical examination to screen for psychiatric health disorders, substance abuse, and chronic pain conditions. Establishing patient expectations with regards to treatment-related outcomes during the preoperative consultation will ensure congruency between the patient and performing surgeon. Patients with a more significant psychiatric distress related to their underlying sexual dysfunction may require additional evaluation and counseling preoperatively. Conclusions: PP placement is associated with high levels of overall satisfaction in appropriately screened patients. Specific considerations during preoperative counseling and careful patient selection, intraoperative decision making to avoid or anticipate possible complications, and postoperative cares are necessary to ensure the best result for an individual patient.

Adult Outcomes of Children With Reactive Attachment Disorder in a Non-Institutionalized Sample.

Objective: Research on reactive attachment disorder (RAD) has focused on institutionalized samples, and long-term outcomes have not been described. This study examines the natural history of RAD into adulthood in a US community sample.Methods: The electronic medical record of a tertiary care center was reviewed for individuals who received an ICD-9 or ICD-10 diagnosis of RAD between 3-12 years old and were ≥ 18 years old at the start of the study; data were collected between February and June 2018. Children with RAD (n = 49) were identified and psychiatric, social, and medical outcomes were collected in childhood and adulthood. A subset of the RAD cohort with comorbid attention-deficit/hyperactivity disorder (ADHD) based on ICD codes (n = 34) was compared with age-matched controls with ADHD and without attachment disorders (n = 102).Results: Children with RAD had high rates of adult psychiatric diagnoses (73.5%), substance use (42.9%), suicide attempts (28.6%), and psychiatric hospitalizations (71.4%). They also demonstrated poor psychosocial outcomes, including low high school (34.7%) and college (2.0%) graduation, high unemployment (26.5%), state-funded health insurance (65.3%), and legal issues (34.7%). Compared to children with ADHD alone, children with RAD and ADHD had higher rates of comorbid adult psychiatric diagnoses (OR 3.0, P = .02), suicide attempts (OR 7.5, P < .01), and hospitalizations (OR 6.4, P < .01).Conclusions: This study describes the natural history of RAD into adulthood in a non-institutionalized sample. The findings suggest that children with RAD have a high burden of psychiatric comorbidities and reduced psychosocial functioning into adulthood that extend beyond the impairment associated with ADHD, a common comorbidity in RAD. These findings highlight the continuous impact of early attachment difficulties on the developmental trajectory of children.

Real-World Clinical Practice Among Patients With Bipolar Disorder and Chronic Kidney Disease on Long-term Lithium Therapy.

PURPOSE: Long-term lithium therapy (LTLT) has been associated with chronic kidney disease (CKD). We investigated changes in clinical characteristics, pharmacotherapeutic treatments for medical/psychiatric disorders, and outcomes among patients with bipolar disorder (BD) and CKD on LTLT in a 2-year mirror-image study design. METHODS: Adult BD patients on LTLT for ≥1 year who enrolled in the Mayo Clinic Bipolar Disorder Biobank and developed CKD (stage 3) were included, and our study was approved by the Mayo Clinic Institutional Review Board. The primary outcome was the time to the first mood episode after CKD diagnosis among the lithium (Li) continuers and discontinuers. Cox proportional hazards models were used to estimate the time to the first mood episode. We tested for differences in other medication changes between the Li continuers and discontinuers group using Mantel-Haenszel χ2 tests (linear associations). RESULTS: Of 38 BD patients who developed CKD, 18 (47%) discontinued Li, and the remainder continued (n = 20). The median age of the cohort was 56 years (interquartile range [IQR], 48-67 years), 63.2% were female, and 97.4% were White. As compared with continuers, discontinuers had more psychotropic medication trials (6 [IQR, 4-6] vs 3 [IQR, 2-5], P = 0.02), a higher rate of 1 or more mood episodes (61% vs 10%, P = 0.002), and a higher risk of a mood episode after CKD diagnoses (Hazard Ratio, 8.38; 95% confidence interval, 1.85-38.0 [log-rank P = 0.001]]. CONCLUSIONS: Bipolar disorder patients on LTLT who discontinued Li had a higher risk for relapse and a shorter time to the first mood episode, suggesting a need for more thorough discussion before Li discontinuation after the CKD diagnosis.

Cardiometabolic and endocrine comorbidities in women with bipolar disorder: A systematic review.

INTRODUCTION: Bipolar Disorder (BD) is known to be equally distributed among males and females. The well-documented increased risk of medical comorbidities in patients with BD, in comparison to BD patients without medical comorbidities, shows a negative impact on the course of illness. There is some evidence suggesting that women with BD have higher psychiatric and medical comorbidities in comparison to men with BD, however there is no evidence in comparison to women without BD or other major psychiatric illness. These comorbidities, along with various psychosocial factors, are known to affect the course of BD. METHODS: We aimed to systematically review the literature on cardiovascular, metabolic and endocrine comorbidities in women with BD in comparison to men with BD and control women. A comprehensive search of electronic databases including PubMed, PsycINFO, Embase, and SCOPUS was conducted, and a total of 61 identified studies were included in this review. RESULTS: Women with BD had higher rates of cardiovascular risk factors/mortality, diabetes mellitus II and thyroid disorders compared to women in the general population. In comparison to men with BD, women with BD had comparable cardiovascular risk but higher prevalence of metabolic and thyroid disorders. LIMITATIONS: Gender specific data was limited in multiple studies. CONCLUSIONS: Results present a need for gender-specific screening and interventions for various medical comorbidities in patients with BD.

Quantification of diet quality utilizing the rapid eating assessment for participants-shortened version in bipolar disorder: Implications for prospective depression and cardiometabolic studies.

OBJECTIVES: Recognizing bipolar disorder as a multi-system metabolic condition driven, in part, by binge eating behavior and atypical depressive symptoms, this study aimed to quantify diet quality and evaluate clinical correlates in a bipolar disorder cohort. METHODS: Participants from the Mayo Clinic Bipolar Disorder Biobank (n = 734) completed the Rapid Eating Assessment for Participants - Shortened version (REAP-S) to determine diet quality. The average REAP-S score for a U.S. omnivorous diet is 32 (range 13 to 39) with higher scores indicating healthier diet. Demographic variables were collected in a standardized clinical questionnaire. Depressive symptoms were assessed by the Bipolar Inventory of Symptoms Scale. Cardiometabolic variables were retrieved from the electronic health record. Associations between continuous variables and REAP-S scores (total, 'healthy foods' and 'avoidance of unhealthy foods') were assessed using linear regression. RESULTS: Overall, our sample had a mean REAP-S score of 27.6 (4.9), suggestive of a lower diet quality than the average general population in the US. There was a significant inverse relationship between mean REAP-S lower scores with increased BMI, waist circumference, disordered eating and depression. All these associations were significantly stronger in female participants. LIMITATIONS: EHR cross-sectional data. CONCLUSIONS: Our data suggest unhealthy diet quality in bipolar disorder is associated with depression, obesity and cardiometabolic abnormalities. Additional work is encouraged to prospectively track mood and diet quality to further understand the bidirectional relationship and clarify if dietary interventions can positively impact mood. Further delineating potential sex differences in diet quality and depression may provide greater appreciation of modifiable risk factors for future cardiometabolic burden.

Clinical and Genetic Correlates of Bipolar Disorder With Childhood-Onset Attention Deficit Disorder.

Background: Bipolar disorder (BD) with co-occurring attention deficit-hyperactivity disorder (ADHD) is associated with an unfavorable course of illness. We aimed to identify potential clinical and genetic correlates of BD with and without ADHD. Methods: Among patients with BD (N = 2,198) enrolled in the Mayo Clinic Bipolar Biobank we identified those with ADHD diagnosed in childhood (BD+cADHD; N = 350), those with adult-onset attention deficit symptoms (BD+aAD; N = 254), and those without ADHD (N = 1,594). We compared the groups using linear or logistic regression adjusting for age, sex, and recruitment site. For genotyped patients (N = 1,443), logistic regression was used to compare ADHD and BD polygenic risk scores (PRSs) between the BD groups, as well as to non-BD controls (N = 777). Results: Compared to the non-ADHD BD group, BD+cADHD patients were younger, more often men and had a greater number of co-occurring anxiety and substance use disorders (all p < 0.001). Additionally, BD+cADHD patients had poorer responses to lithium and lamotrigine (p = 0.005 and p = 0.007, respectively). In PRS analyses, all BD patient subsets had greater genetic risk for BD and ADHD when compared to non-BD controls (p < 0.001 in all comparisons). BD+cADHD patients had a higher ADHD-PRS than non-ADHD BD patients (p = 0.012). However, BD+aAD patients showed no evidence of higher ADHD-PRS than non-ADHD BD patients (p = 0.38). Conclusions: BD+cADHD was associated with a greater number of comorbidities and reduced response to mood stabilizing treatments. The higher ADHD PRS for the BD+cADHD group may reflect a greater influence of genetic factors on early presentation of ADHD symptoms.

Persistent Genital Arousal Disorder (PGAD): A Clinical Review and Case Series in Support of Multidisciplinary Management.

INTRODUCTION: Persistent genital arousal disorder (PGAD) is an uncommon condition resulting in intrusive, unwanted and distressing symptoms of genital arousal. Presentation can vary and most cases do not have an immediately identifiable etiology. OBJECTIVES: To present evaluation and treatment recommendations for PGAD from a multidisciplinary perspective and provide case examples. METHODS: A focused review of the literature on diagnosis, workup, and treatment of PGAD was completed. A case series of 3 varying presentations of PGAD is offered. RESULTS: PGAD results in high levels of patient distress and is best managed with a multidisciplinary treatment approach. Identification and management of co-occurring symptoms or disease states is imperative, particularly psychologic and psychiatric comorbidities. With appropriate intervention, patients may achieve improvement of their physical symptoms and a decrease in associated psychological distress. CONCLUSION: PGAD is an uncommon and highly distressing condition that requires thoughtful evaluation for appropriate diagnosis and treatment. Multidisciplinary treatment approaches provide the best opportunity to address the needs of patients and optimizing treatment response. Pease ER, Ziegelmann M, Vencill JA, et al. Persistent Genital Arousal Disorder (PGAD): A Clinical Review and Case Series in Support of Multidisciplinary Management. Sex Med Rev 2022;10:53-70.

Association of Optimal Lamotrigine Serum Levels and Therapeutic Efficacy in Mood Disorders: A Systematic Review.

PURPOSE: The aim of the study was to appraise the current evidence on the optimal serum level for lamotrigine (LAM) in the treatment of mood disorders (major depressive disorder, bipolar disorder). METHODS: Major databases were searched for randomized controlled trials, open-label trials, and observational studies reporting serum LAM levels in adult patients treated with LAM for mood disorders. RESULTS: A total of 814 abstracts were screened and 24 articles were selected for full-text review. Seven studies (226 bipolar disorder and 17 major depressive disorder patients) including 1 randomized controlled trial (n = 43), 3 prospective (n = 53), and 3 retrospective (n = 147) studies met the study criteria with a study duration range from 6 to 96 weeks. Lamotrigine daily dosage varied from 25 to 425 mg/d among the studies. Studies reported inconsistent findings between LAM concentration and efficacy. Three studies did not identify a relationship between LAM levels and a significant improvement in mood symptoms. Two studies (n = 99) reported higher response rates with LAM serum levels of greater than 3.25 µg/mL and 1 study (n = 25) reported a wide therapeutic window of 5 to 11 µg/mL. Overall, LAM was well tolerated with no major significant adverse effects. CONCLUSIONS: Most studies showed a minimum LAM threshold level of 3 µg/mL in patients with mood disorders; however, the data are inconsistent regarding the therapeutic range for LAM. Based on the pooled data, there is inconsistent evidence to make conclusive recommendations on therapeutic LAM serum levels for mood improvement. Further studies including larger sample sizes are required to address this relevant clinical question.

Perinatal Mood and Anxiety Disorder Management in Multicenter Community Practices: Clinicians' Training, Current Practices and Perceived Strategies to Improve Future Implementation.

BACKGROUND: This study aimed to explore clinicians' perspectives on the current practice of perinatal mood and anxiety disorder (PMAD) management and strategies to improve future implementation. METHODS: This study had a cross-sectional, descriptive design. A 35-item electronic survey was sent to clinicians (N = 118) who treated perinatal women and practiced at several community clinics at an academic medical center in the United States. RESULTS: Among clinicians who provided care for perinatal women, 34.7% reported never receiving PMAD management training and 66.3% had less than 10 years of experience. Out of 10 patients who reported psychiatric symptoms, 47.8% of clinicians on average reported providing PMAD management to 1 to 3 patients and 40.7% noted that they conducted screening only when patient expresses PMAD symptoms. Suggested future improvements were providing training, developing a referral list, and establishing integrated behavioral health services. CONCLUSIONS: Results from this study indicated that while PMAD screening and management was implemented, improvements are warranted to meet established guidelines. Additionally, clinicians endorsed providing PMAD management to a small percentage of perinatal patients. Suggested strategies to increase adoption and implementation of PMAD management should be explored to improve access to behavioral health services for perinatal women.

Long-term lithium therapy and risk of chronic kidney disease in bipolar disorder: A historical cohort study.

AIMS: Long-term lithium therapy (LTLT) has been associated with kidney insufficiency in bipolar disorder (BD). We aimed to investigate the risk factors of chronic kidney disease (CKD) development and progression among BD patients receiving LTLT. METHODS: We included adult patients with BD on LTLT (≥1 year) who were enrolled in the Mayo Clinic Bipolar Biobank, Rochester, Minnesota. We reviewed electronic medical records to extract information related to lithium therapy and kidney-related data to assess changes in the estimated glomerular filtration rate (eGFR). CKD severity was assessed based on eGFR. RESULTS: Among 154 patients who received LTLT, 41 patients (27%) developed CKD, of whom 20 (49%) patients continued lithium (continuers) and 19 (46%) discontinued it (discontinuers). The median time to stage 3 CKD development was 21.7 years from the start of Li treatment. Type-2 diabetes mellitus and benzodiazepine use were independent predictors for CKD development in the survival analysis, after controlling for age. The subsequent CKD progression rate did not differ between continuers and discontinuers (mean GFR 48.6 vs. 44.1, p = 0.13) at the end of follow-up duration (mean duration: 3.5 ± 4.4 years for continuers and 4.9 ± 5.3 years for discontinuers). CONCLUSION: CKD was observed in one fourth of patients with BD receiving LTLT. There was no significant difference in the progression of CKD among Li continuers versus discontinuers, at the mean follow-up duration of 4.2 years, after the CKD diagnosis. Progression of CKD could be influenced by existing comorbidities and may not necessarily be due to lithium alone.

Contraception for Women With Psychiatric Disorders.

OBJECTIVE: Mental health care for women includes decision support to prepare for major life events, including preconception planning for treatment during pregnancy and the postpartum period. The authors discuss contraceptive choices and their effectiveness, side effects, and impact on psychiatric symptoms. The Centers for Disease Control and Prevention's recommendations, Medical Eligibility Criteria for Contraceptive Use, provided the structure for review of contraceptive choices. METHODS: A search of PsycINFO, PubMed, Embase, and Scopus was conducted for publications on the management of contraception for women with mental illness. Publications were selected if they included, based on the authors' consensus, data supporting evidence-based care important for psychiatrists who treat women desiring contraceptives. RESULTS: The majority of women choose combined oral contraceptives. Although long-acting reversible contraceptives (implants, intrauterine devices) are associated with low failure rates, favorable safety profiles, rapid return to fertility after removal, and few contraindications, they are chosen by only 14% of women. All methods are acceptable for women with depression, although medical comorbidities may dictate a specific type. The impact of hormonal contraceptives on the risk for depression is controversial; however, clinical studies and randomized placebo-controlled trials of women with psychiatric disorders have generally reported similar or lower rates of mood symptoms in hormonal contraceptive users compared with nonusers. Although interactions between psychotropic drugs and contraceptives are rare, clozapine, anticonvulsants, and St. John's Wort are exceptions. CONCLUSIONS: Proactive management of mental illness, contraception, and pregnancy improves a woman's capacity to function and optimizes her mental and reproductive health.

Potential pharmacogenomic targets in bipolar disorder: considerations for current testing and the development of decision support tools to individualize treatment selection.

BACKGROUND: Treatment in bipolar disorder (BD) is commonly applied as a multimodal therapy based on decision algorithms that lack an integrative understanding of molecular mechanisms or a biomarker associated clinical outcome measure. Pharmacogenetics/genomics study the individual genetic variation associated with drug response. This selective review of pharmacogenomics and pharmacogenomic testing (PGT) in BD will focus on candidate genes and genome wide association studies of pharmacokinetic drug metabolism and pharmacodynamic drug response/adverse event, and the potential role of decision support tools that incorporate multiple genotype/phenotype drug recommendations. MAIN BODY: We searched PubMed from January 2013 to May 2019, to identify studies reporting on BD and pharmacogenetics, pharmacogenomics and PGT. Studies were selected considering their contribution to the field. We summarize our findings in: targeted candidate genes of pharmacokinetic and pharmacodynamic pathways, genome-wide association studies and, PGT platforms, related to BD treatment. This field has grown from studies of metabolizing enzymes (i.e., pharmacokinetics) and drug transporters (i.e., pharmacodynamics), to untargeted investigations across the entire genome with the potential to merge genomic data with additional biological information. CONCLUSIONS: The complexity of BD genetics and, the heterogeneity in BD drug-related phenotypes, are important considerations for the design and interpretation of BD PGT. The clinical applicability of PGT in psychiatry is in its infancy and is far from reaching the robust impact it has in other medical disciplines. Nonetheless, promising findings are discovered with increasing frequency with remarkable relevance in neuroscience, pharmacology and biology.

Amphetamine/Dextroamphetamine Salts for Delayed Orgasm and Anorgasmia in Men: A Pilot Study.

OBJECTIVE: To describe our experience with amphetamine/dextroamphetamine salts (AMP) as a treatment for delayed orgasm/anorgasmia (DO/AO). METHODS: We identified patients with DO/AO from September 2017 to September 2019. Baseline characteristics and patient-reported orgasmic latency time (OLT) were recorded. After extensive screening, patients were treated with AMP. Validated questionnaires were administered including International Index of Erectile Function, quantitative Androgen Deficiency in the Aging Male and Adult ADHD Self-Report Scale. OLT change, adverse effects, and patient satisfaction were assessed. Baseline characteristics were compared using chi-squared test. OLT changes were compared with one-way ANOVA. Multivariable logistic regression was performed to identify predictors of treatment success. P < 0.05 was statistically significant. RESULTS: Seventeen men received AMP - 6 of 17 (35.3%) for AO and 11 of 17 (64.7%) for DO, with median follow-up 1.0 year (interquartile range [IQR] 1.0 year). Amongst responders, AMP improved subjective experience of sex in 8 of 17 (47.1%) patients (2/6 with AO). Of those, 6 of 17 (35.3%; 1/6 with AO) experienced reduced OLT or increased frequency of orgasm. Non-responders were older than responders, with median age 69.5 (IQR 4.3) vs 61.0 years (IQR 12.3; P = 0.024). There were no other significant differences in baseline characteristics among responders. Of note, 6 of 8 (75%) responders and 8 of 9 (88.9%) non-responders failed other treatment modalities prior to AMP. Among responders with DO and improved OLT, mean OLT decreased by 72.3% (40.7 to 11.1 minutes, P = 0.049) during intercourse. Minimal side effects were noted including insomnia and jitters, each in one patient respectively. CONCLUSION: AMP as a treatment for AO/DO merits further investigation. Measurable improvements in OLT or frequency of orgasm occurred in more than a third of patients. Larger prospective multicenter studies with strict inclusion and exclusion criteria are warranted.