Management dilemma: managing bipolar affective disorder in a patient with hereditary angioedema.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by the deficiency or dysfunction of C1 esterase inhibitors. We present a case of a female in her 50s with HAE and bipolar affective disorder (BPAD). She has experienced severe depressive and manic episodes with significant disruption to her life. She has also had potentially life-threatening episodes of recurrent angioedema with severe facial and body swelling and post-pharyngeal symptoms.She presented to us with a depressive episode with suicidal ideation. Her angioedema was flared by both psychological stressors and psychotropic medications. Choosing the correct mood stabiliser without triggering angioedema was a major challenge in her treatment. Also, psychosocial interventions and frequent liaison with her immunology team were necessary to provide her with optimum care in the community. Here, we discuss the challenges we faced and how we overcame them in managing this rare presentation of coexisting BPAD and HAE.

Full-spectrum efficacy of cariprazine across manic and depressive symptoms of bipolar I disorder in patients experiencing mood episodes: Post hoc analysis of pooled randomized controlled trial data.

INTRODUCTION: Patients with bipolar I disorder may experience mood destabilization or treatment-emergent affective switch (TEAS) from one symptom pole to the other spontaneously or following treatment. Optimal treatment should address symptoms from both poles without precipitating destabilization. METHODS: These were pooled post hoc analyses of data from randomized, double-blind, placebo-controlled studies of cariprazine 3-12 mg/d for bipolar I mania (NCT00488618, NCT01058096, NCT01058668) and cariprazine 1.5 mg/d or 3 mg/d for bipolar I depression (NCT01396447, NCT02670538, NCT02670551). Changes from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 6 and Young Mania Rating Scale (YMRS) total score at week 3 were analyzed in each indication using a mixed-effects model for repeated measures. Percentages of patients with increasing levels of endpoint response and TEAS (bipolar mania = MADRS total score ≥ 19; bipolar depression = YMRS score ≥ 16) were determined. RESULTS: Cariprazine significantly reduced manic and depressive symptoms in patients with bipolar I disorder mood episodes. In patients with a manic episode and up to mild baseline depressive symptoms, cariprazine also significantly reduced depressive symptoms. In patients with a depressive episode and manic symptoms in remission at baseline, numerical reduction (without statistical significance) in YMRS indicated no worsening of mania. In both indications, cariprazine-treated patients had numerically greater response rates (presenting symptom pole) than placebo-treated patients; lower percentages of cariprazine- than placebo-treated patients had TEAS at visits where data were collected. LIMITATIONS: Post hoc analysis. CONCLUSION: Results suggested that cariprazine had full-spectrum efficacy across symptoms from both poles in patients with bipolar I disorder mood episodes; TEAS risk was low. Patient-level response suggested that improvement was clinically relevant.

Comparing suicide completion rates in bipolar I versus bipolar II disorder: A systematic review and meta-analysis.

BACKGROUND: Bipolar disorder (BD) has a high disease burden and the highest mortality risk in BD comes from suicide. Bipolar disorder type II (BD-II) has been described as a milder form of bipolar disorder; however, extant literature is inconsistent with this description and instead describe illness burden and notably suicidality comparable to persons with bipolar I disorder (BD-I). Towards quantifying the hazard of BD-II, herein we aim via systematic review and meta-analysis to evaluate the rates of completed suicide in BD-I and BD-II. METHOD: We conducted a literature search on PubMed, OVID (Embase, Medline) and PsychINFO databases from inception to June 30th, 2023, according to PRISMA guidelines. Articles were selected based on the predetermined eligibility criteria. A meta-analysis was performed, comparing the risk of completed suicide between individuals diagnosed with BD-I to BD-II. RESULTS: Four out of eight studies reported higher suicide completion rates in persons living with BD-II when compared to persons living with BD-I; however, two of the studies reported non-significance. Two studies reported significantly higher suicide completion rates for BD-I than BD-II. The pooled odds ratio of BD-II suicide rates to BD-I was 1.00 [95 % CI = 0.75, 1.34]. LIMITATIONS: The overarching limitation is the small number of studies and heterogeneity of studies that report on suicide completion in BD-I and BD-II. CONCLUSION: Our study underscores the severity of BD-II, with a risk for suicide not dissimilar from BD-I. The greater propensity to depression, comorbidity and rapid-cycling course reported in BD-II are contributing factors to the significant mortality hazard in BD-II.

Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach.

BACKGROUND AND HYPOTHESIS: Investigating the shared brain protein and genetic components of schizophrenia (SCZ) and bipolar I disorder (BD-I) presents a unique opportunity to understand the underlying pathophysiological processes and pinpoint potential drug targets. STUDY DESIGN: To identify overlapping susceptibility brain proteins in SCZ and BD-I, we carried out proteome-wide association studies (PWAS) and Mendelian Randomization (MR) by integrating human brain protein quantitative trait loci with large-scale genome-wide association studies for both disorders. We utilized transcriptome-wide association studies (TWAS) to determine the consistency of mRNA-protein dysregulation in both disorders. We applied pleiotropy-informed conditional false discovery rate (pleioFDR) analysis to identify common risk genetic loci for SCZ and BD-I. Additionally, we performed a cell-type-specific analysis in the human brain to detect risk genes notably enriched in distinct brain cell types. The impact of risk gene overexpression on dendritic arborization and axon length in neurons was also examined. STUDY RESULTS: Our PWAS identified 42 proteins associated with SCZ and 14 with BD-I, among which NEK4, HARS2, SUGP1, and DUS2 were common to both conditions. TWAS and MR analysis verified the significant risk gene NEK4 for both SCZ and BD-I. PleioFDR analysis further supported genetic risk loci associated with NEK4 for both conditions. The cell-type specificity analysis revealed that NEK4 is expressed on the surface of glutamatergic neurons, and its overexpression enhances dendritic arborization and axon length in cultured primary neurons. CONCLUSIONS: These findings underscore a shared genetic origin for SCZ and BD-I, offering novel insights for potential therapeutic target identification.

Early improvement with cariprazine as a predictor of antidepressant, anxiolytic, and antimanic response in bipolar I mania and depression: A pooled post hoc analysis of randomized cariprazine trials.

BACKGROUND: Early symptomatic improvement may predict treatment response in bipolar I disorder. Cariprazine has demonstrated early treatment effects in bipolar I depression and mania studies; therefore, we assessed whether early improvement with cariprazine predicts eventual treatment response. METHODS: Post hoc analyses used pooled data from randomized, double-blind, placebo-controlled bipolar I depression (NCT02670538, NCT02670551) and mania (NCT00488618, NCT01058096, NCT01058668) trials. In depression studies (cariprazine 1.5 mg/d, 3 mg/d, or placebo), early improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) total scores (≥25 % improvement at day 15) and subsequent depressive/anxiety symptom response status (≥50 % improvement at week 6) were assessed. In mania studies (cariprazine 3-12 mg/d or placebo), early improvement in Young Mania Rating Scale (YMRS) total scores (≥25 % improvement at day 7) and manic symptom response status (≥50 % improvement at week 3) were assessed. RESULTS: Patients with bipolar I depression and early MADRS improvement were approximately 4- to 6-times as likely to achieve MADRS or HAM-A response than those without early improvement; patients with early HAM-A improvement were approximately 3- to 4-times as likely to achieve MADRS or HAM-A response. A subset of patients without early improvement with cariprazine 1.5 mg/d (20 %-31 %) subsequently responded following up-titration. Patients with mania and early YMRS improvement were approximately 5 times more likely to have manic symptom response than those without early improvement. LIMITATIONS: Post hoc analysis; relatively short study durations; flexible-dosing (mania studies). CONCLUSIONS: Early symptom improvement with cariprazine may inform therapeutic decisions for patients with bipolar I disorder.

Cognition in Euthymic Patients with Bipolar Disorder: Do Not Forget to Account for Anxiety!

Purpose: Despite the high prevalence of anxiety disorders in BD and its known impact on cognitive performance, the presence and severity of anxious symptoms is not systematically evaluated in studies on cognition in BD. Our aim was to determine if attention and/or inhibition of cognitive interference in euthymic patients with type I Bipolar Disorder (BD-I) is affected by symptoms of anxiety. Patients and Methods: Eighty-seven euthymic BD-I patients were included. Patients with comorbidities other than Generalized Anxiety Disorder (GAD) or Panic Disorder (PD) were excluded. State anxiety was measured with the Brief Inventory of Anxious Responses and Situations (ISRA-B). Subjective cognitive performance was evaluated with the COBRA scale, attention with the Digit-Span Forward task and inhibition of cognitive interference was assessed with the StroopTest interference score. Multiple linear regression models were used to test if anxious symptoms were associated with attention or inhibition of cognitive interference, considering other known contributors for cognitive impairment. Results: Attention was unaffected by anxiety symptoms, but the overall regression for inhibition of cognitive interference was significant: years of schooling (ß=1.12, p = 0.001), cognitive complaints (ß=0.44, p = 0.008), and anxiety (ß=-0.21, p = 0.017) explained 15% of the interference score of the Stroop test (R2 = 0.15). Conclusion: Beyond residual affective symptoms, anxious symptoms seem to affect inhibition of cognitive interference. We recommend routine testing of anxiety when considering cognitive evaluations, especially when screening for cognitive deficits.

Navigating Treatment Challenges: A Case Study on Refractory Psychosis in a Chronic MDMA (3,4-Methylenedioxymethamphetamine) User.

MDMA (3,4-methylenedioxy​methamphetamine), also known as Ecstasy, is a synthetic amphetamine with hallucinogenic and stimulant properties, which has become increasingly favored as a substance for recreational use. Despite its deceptive reputation as "safe," chronic MDMA use is associated with neuropsychiatric complications, including psychosis. We describe a case of a 23-year-old woman with chronic MDMA use disorder and childhood trauma, who presented with severe psychosis and catatonic features. While initial diagnostic possibilities included drug-induced psychosis and mood disorders, the patient's history and presentation supported a diagnosis of bipolar I disorder with psychotic features, which was exacerbated by MDMA use. Conventional antipsychotics failed to improve psychotic symptoms and led to worsening of catatonia, requiring electroconvulsive therapy (ECT) for improvement. Socioeconomic barriers hindered follow-up care, leading to an Emergency Department (ED) admission shortly after discharge. This case highlights the intricate interplay between substance use, psychiatric illness, and trauma, and showcases ECT's efficacy in severe psychosis. It emphasizes the necessity for comprehensive mental health services, especially for vulnerable populations, and calls for further research into MDMA's psychiatric effects and optimal treatment approaches for individuals with co-occurring substance use and psychiatric disorders.

Pharmacologic Treatment of Malignant Catatonia Without Electroconvulsive Therapy: A Case Report.

Malignant catatonia is a rare, life-threatening variant of catatonia requiring prompt treatment. Malignant catatonia is characterized by typical catatonia symptoms of psychomotor, neurologic, and behavioral changes complicated by autonomic instability, with an estimated mortality rate of 50% or more when untreated. Electroconvulsive therapy (ECT) is considered the definitive and most effective treatment for malignant catatonia, with minimal literature on the efficacy of pharmacological interventions alone. Timely access to life-saving ECT may be limited in some hospitals due to restrictive laws on the use of ECT when the patient is incapacitated or due to lack of treatment availability. This case report describes the successful pharmacologic treatment of a patient with malignant catatonia where ECT was unobtainable due to legal restrictions and lack of access to treatment. The patient was initially commenced on lorazepam but continued to deteriorate, subsequently developing complications of aspiration pneumonia and Clostridium difficile colitis. The patient's malignant catatonia resolved with a combination of lorazepam, memantine, and a one-time dose of dantrolene. This complex case highlights the challenges of treating malignant catatonia in under-resourced systems or jurisdictions with restrictive ECT laws and adds additional data on the successful use of pharmacologic interventions for malignant catatonia where ECT is impractical or delayed.

Clinical distinctions in symptomatology and psychiatric comorbidities between misdiagnosed bipolar I and bipolar II disorder versus major depressive disorder.

BACKGROUND: To explore the demographic and clinical features of current depressive episode that discriminate patients diagnosed with major depressive disorder (MDD) from those with bipolar I (BP-I) and bipolar II (BP-II) disorder who were misdiagnosed as having MDD . METHODS: The Mini-International Neuropsychiatric Interview (MINI) assessment was performed to establish DSM-IV diagnoses of MDD, and BP-I and BP-II, previously being misdiagnosed as MDD. Demographics, depressive symptoms and psychiatric comorbidities were compared between 1463 patients with BP-I, BP-II and MDD from 8 psychiatric settings in mainland China. A multinomial logistic regression model was performed to assess clinical correlates of diagnoses. RESULTS: A total of 14.5% of the enrolled patients initially diagnosed with MDD were eventually diagnosed with BP. Broad illness characteristics including younger age, higher prevalence of recurrence, concurrent dysthymia, suicidal attempts, agitation, psychotic features and psychiatric comorbidities, as well as lower prevalence of insomnia, weight loss and somatic symptoms were featured by patients with BP-I and/or BP-I, compared to those with MDD. Comparisons between BP-I and BP-II versus MDD indicated distinct symptom profiles and comorbidity patterns with more differences being observed between BP-II and MDD, than between BP-I and MDD . CONCLUSION: The results provide evidence of clinically distinguishing characteristics between misdiagnosed BP-I and BP- II versus MDD. The findings have implications for guiding more accurate diagnoses of bipolar disorders.

Significant improvements in the olfactory sensitivity of bipolar I disorder patients during euthymia versus manic episodes: a longitudinal study.

Introduction: Research has indicated that individuals diagnosed with bipolar disorder (BD) might experience alterations in their olfaction or levels of serum tumor necrosis factor-α (TNF-α), but no studies have investigated olfactory function and serum TNF-α in BD patients simultaneously. Moreover, there is a lack of existing research that compares the longitudinal olfactory function between individuals with manic and euthymic BD I. Methods: Patients with manic BD I (BDM, n=44) and healthy controls (HCs, n=32) were evaluated symptoms (measured via the Young Manic Rating Scale, YRMS), social function (measured via the Global Assessment Function, GAF), serum TNF-α, and olfactory function (via the Sniffin' Sticks test) including olfactory sensitivity (OS) and olfactory identification (OI). The BDM patients were followed up to the remission period and re-evaluated again. We compared OS, OI and serum TNF-α in manic and euthymic patients with BD I and HCs. We examined the correlation between olfactory function and symptoms, social function, and serum TNF-α in patients with BD I. Results: The BDM patients exhibited significantly lower OS and OI compared to the HCs (Z = -2.235, P = 0.025; t = -6.005, P < 0.001), while a positive correlation was observed between OS and GAF score (r = 0.313, P = 0.039). The OS in the BD I remission group (n=25) exhibited significantly superior performance compared to the BDM group (t = -4.056, P < 0.001), and the same as that in the HCs (P = 0.503). The change in OS showed a positive correlation with the decrease in YMRS score (r = 0.445, P = 0.026), and a negative correlation with the course of disease (r = -0.594, P = 0.002). The TNF-α in BD I patients was significantly lower compared to HCs (P < 0.001), and not significantly correlated with olfactory function (all P > 0.05). Conclusion: The findings suggest that OS and OI are impaired in BDM patients, and the impaired OS in those patients can be recovered in the remission stage. OI may serve as a potential characteristic marker of BD. OS might be useful as an index for BDM treatment efficacy and prognosis.

Oculomotor Abnormalities and Aberrant Neuro-Developmental Markers: Composite Endophenotype for Bipolar I Disorder: Anomalies Oculomotrices et Marqueurs Neuro-Développementaux Aberrants : Endophénotype Composite du Trouble Bipolaire I.

BACKGROUND: Neurological soft signs (NSSs), minor physical anomalies (MPAs), and oculomotor abnormalities were plausible biomarkers in bipolar disorder (BD). However, specific impairments in these markers in patients after the first episode mania (FEM), in comparison with first-degree relatives (high risk [HR]) of BD and healthy subjects (health control [HC]) are sparse. AIM OF THE STUDY: This study aimed at examining NSSs, MPAs, and oculomotor abnormalities in remitted adult subjects following FEM and HR subjects in comparison with matched healthy controls. Investigated when taken together, could serve as composite endophenotype for BD. METHODS: NSSs, MPAs, and oculomotor abnormalities were evaluated in FEM (n = 31), HR (n = 31), and HC (n = 30) subjects, matched for age (years) (p = 0.44) and sex (p = 0.70) using neurological evaluation scale, Waldrop's physical anomaly scale and eye tracking (SPEM) and antisaccades (AS) paradigms, respectively. RESULTS: Significant differences were found between groups on NSSs, MPAs, and oculomotor parameters. Abnormalities are higher in FEM subjects compared to HR and HC subjects. Using linear discriminant analysis, all 3 markers combined accurately classified 72% of the original 82 subjects (79·2% BD, 56·70% HR, and 82·1% HC subjects). CONCLUSIONS: AS and SPEM could enhance the utility of NSSs, and MPAs as markers for BD. The presence of these abnormalities in FEM suggests their role in understanding the etiopathogenesis of BD in patients who are in the early course of illness. These have the potential to be composite endophenotypes and have further utility in early identification in BD.

Eye movement abnormalities and Atypical Neurodevelopmental markers as Composite Measurable components in the pathway between disease manifestation and genetics in Bipolar I Disorder.

Returning to college after inpatient psychiatric treatment: a case study of bipolar I disorder management.

Bipolar disorder is typically diagnosed in the teenage to early adulthood years. During this age, many individuals are students pursuing a college degree. Students developing the symptoms of bipolar disorder have a harder time navigating college and have significant difficulties transitioning back to school after psychiatric hospitalization, potentially influencing quality of life. Despite this, little attention has been given to the academic needs of hospitalized college students. This paper discusses the case of a 21-year-old female with a history of bipolar I disorder who was hospitalized for treatment of a manic episode. We discuss interventions to accommodate her educational needs during hospitalization to help minimize her academic load and ease her transition back to college. With this case study, we address the lack of well-established systems to reacclimate hospitalized college students and propose solutions to mitigate the hardships of transitioning from hospitalization back to the rigors of being a student.

Possible association between lithium intoxication and Takotsubo syndrome.

More than 25 years after being diagnosed with bipolar disorder and receiving continuous treatment with lithium, a woman develops Takotsubo syndrome.

Differences in clinical presentation between newly diagnosed bipolar I and II disorders: A naturalistic study.

AIM: This naturalistic clinical study aims to investigate differences between newly diagnosed patients with bipolar type I (BDI) and bipolar type II (BDII) disorders in socio-demographic and clinical characteristics, affective symptoms, cognition, functioning and comorbidity with personality disorders. METHODS: The BD diagnosis and type were confirmed using the Schedules for Clinical Assessment in Neuropsychiatry. Affective symptoms were assessed with the Young Mania Rating Scale, the Hamilton Depression Rating Scale, the Major Depressive Index, and the Altman Self-Rating Mania Scale. Functional impairment was assessed with the Functional Assessment Short Test. Cognitive impairment was evaluated by the Screen for Cognitive Impairment in Psychiatry and the Cognitive Complaints in Bipolar Disorder Rating Assessment. Finally, comorbid personality disorders were assessed with the Standardized Assessment of Personality-Abbreviated Scale and structured interview Structured Clinical Interview for DSM-disorders. RESULTS: 383 newly diagnosed patients were included (BDI: n = 125; BDII: n = 258). Against expectations, we found no more depressive symptoms in BDII compared with BDI nor any differences in cognitive, childhood trauma or overall functional impairment. The only difference was lower occupational impairment in the BDII group. LIMITATIONS: The self-reported measures of cognitive difficulties and childhood trauma involved potential bias (recall or other). Despite BD being newly diagnosed a diagnostic delay was observed. CONCLUSION: Patients newly diagnosed with BDII and BDI had similar burdens of depressive symptoms and cognitive and overall functional impairment, however patients with BDI had lower occupational functioning. No statistically significant difference was found in prevalence of comorbid personality disorders between patients with BDI and BDII.

Occurrence of postpartum manic or mixed episodes in women with bipolar I disorder: A systematic review and meta-analysis.

OBJECTIVE: Accurate information on the frequency and prevalence of manic or mixed episodes is important for therapeutic, prognostic, and safety concerns. We aimed to estimate the risk of relapse of manic and mixed episodes after delivery in women with bipolar I disorder or schizoaffective disorder-bipolar type. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive literature search in PubMed, PsycINFO, Embase, and Cochrane databases was carried out on November 17, 2022, using the terms ((bipolar disorder) OR (manic depressive illness)) AND (mania)) AND (postpartum)) AND (recurrence)) AND (relapse). The search was updated on March 29, 2023. Case studies and qualitative analyses were excluded. Twelve studies reporting on 3595 deliveries in 2183 women were included in the quantitative analysis. RESULTS: The overall pooled estimate of postpartum relapse risk was 39% (95% CI = 29, 49; Q(11) = 211.08, p < 0.001; I2 = 96.31%). Among those who had a relapse, the pooled estimate of risk for manic and mixed episodes was 38% (95% CI = 28, 50; Q(11) = 101.17, p < 0.001; I2 = 91.06%). Using data from the nine studies that reported the percentage of medication use during pregnancy, we estimated a meta-regression model with the percent medication use as a continuous explanatory variable. The estimated prevalence of relapse was 58.1% (95% CI, 9.6 to 39.3 to 76.8) for studies with no medication use and 25.9% (95% CI, 10.5-41.3) for studies with 100% medication use. The difference between the two prevalence estimates was statistically significant, z = -2.099, p = 0.0359. CONCLUSIONS: Our findings suggest an overall pooled estimate of postpartum relapse risk of 39%, while the pooled estimate of risk for manic and mixed episodes was 38%. These findings highlight the need to educate patients with bipolar I disorder, and their healthcare professionals about the high risk of relapse of manic or mixed episodes after delivery.

Aberrant Neurofunctional Responses During Emotional and Attentional Processing Differentiate ADHD Youth With and Without a Family History of Bipolar I Disorder.

OBJECTIVE: To compare neurofunctional responses in emotional and attentional networks of psychostimulant-free ADHD youth with and without familial risk for bipolar I disorder (BD). METHODS: ADHD youth with (high-risk, HR, n = 48) and without (low-risk, LR, n = 50) a first-degree relative with BD and healthy controls (n = 46) underwent functional magnetic resonance imaging while performing a continuous performance task with emotional distracters. Region-of-interest analyses were performed for bilateral amygdala (AMY), ventrolateral (VLPFC) and dorsolateral (DLPFC) prefrontal cortex, and anterior (ACC) and posterior cingulate cortex (PCC). RESULTS: Compared with HC, HR, but not LR, exhibited predominantly left-lateralized AMY, VLPFC, DLPFC, PCC, and rostral ACC hyperactivation to emotional distractors, whereas LR exhibited right VLPFC and bilateral dorsal ACC hypoactivation to attentional targets. Regional responses correlated with emotional and attention symptoms. CONCLUSION: Aberrant neurofunctional responses during emotional and attentional processing differentiate ADHD youth with and without a family history of BD and correlate with relevant symptoms ratings.

Resolving heterogeneity in schizophrenia, bipolar I disorder, and attention-deficit/hyperactivity disorder through individualized structural covariance network analysis.

Disruptions in large-scale brain connectivity are hypothesized to contribute to psychiatric disorders, including schizophrenia, bipolar I disorder, and attention-deficit/hyperactivity disorder. However, high inter-individual variation among patients with psychiatric disorders hinders achievement of unified findings. To this end, we adopted a newly proposed method to resolve heterogeneity of differential structural covariance network in schizophrenia, bipolar I disorder, and attention-deficit/hyperactivity disorder. This method could infer individualized structural covariance aberrance by assessing the deviation from healthy controls. T1-weighted anatomical images of 114 patients with psychiatric disorders (schizophrenia: n = 37; bipolar I disorder: n = 37; attention-deficit/hyperactivity disorder: n = 37) and 110 healthy controls were analyzed to obtain individualized differential structural covariance network. Patients exhibited tremendous heterogeneity in profiles of individualized differential structural covariance network. Despite notable heterogeneity, patients with the same disorder shared altered edges at network level. Moreover, individualized differential structural covariance network uncovered two distinct psychiatric subtypes with opposite differences in structural covariance edges, that were otherwise obscured when patients were merged, compared with healthy controls. These results provide new insights into heterogeneity and have implications for the nosology in psychiatric disorders.

Management of Concurrent Bipolar I Disorder and Compulsive Sexual Behavior Disorder: A Case Report.

Pornography addiction is not currently recognized in the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V), but it can be broadly classified under compulsive sexual behavior disorder (CSBD) in the International Classification for Diseases (ICD). An increased incidence of CSBD has been reported in patients with bipolar I disorder (BPI) as an independent compulsion, not secondary to mania. Due to the ambiguity of identifying pornography addiction in the DSM-V, approved treatment for patients with a concurrent diagnosis of CSBD in the context of BPI is limited. We report the case of a patient with CSBD with concurrent BPI and investigate the treatment strategy taken in an inpatient setting. Though there are no FDA-approved treatment strategies currently approved for patients with concurrent CSBD and BPI, selective serotonin reuptake inhibitors, mood stabilizers, naltrexone, and cognitive behavioral therapy can be used in combination for maximal benefit.

Aripiprazole Plasma Concentrations Delivered from Two 2-Month Long-Acting Injectable Formulations: An Indirect Comparison.

Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a novel long-acting injectable (LAI) formulation of aripiprazole monohydrate for administration once every 2 months, developed for the treatment of schizophrenia or maintenance monotherapy treatment of bipolar I disorder in adults (indication will vary by country). Aripiprazole lauroxil 1064 mg (AL 1064) is an LAI formulation of aripiprazole lauroxil, an aripiprazole prodrug, for administration once every 2 months, indicated for the treatment of schizophrenia in adults. This analysis provides an indirect comparison of aripiprazole plasma concentrations following multiple doses of either formulation. Clinical trial data were used to determine average steady-state aripiprazole plasma concentration (Cavg,ss), maximum aripiprazole plasma concentration (Cmax), and other pharmacokinetic parameters of either formulation following four administrations (96 patients received Ari 2MRTU 960; 28 patients received AL 1064). All pharmacokinetic parameters were considered in the context of a minimum aripiprazole therapeutic concentration (Cmin) of ≥95 ng/mL. An exposure-response analysis using data from two Phase III trials of aripiprazole once-monthly (an aripiprazole monohydrate LAI, administered monthly), showed that patients with a Cmin ≥95 ng/mL are 4.41 times less likely to relapse than patients with a Cmin <95 ng/mL. A similar analysis has not been performed for AL 1064. However, consensus guidelines for therapeutic drug monitoring recommend a range of 100-350 ng/mL for aripiprazole. Following four administrations, mean (standard deviation [SD]) Cavg,ss over the 2-month dosing interval was 263 (133) ng/mL for Ari 2MRTU 960 and 140.7 (57.3) ng/mL for AL 1064. Mean (SD) Cmax during the fourth dosing interval was 342 (157) ng/mL for Ari 2MRTU 960 and 188.8 (79.8) ng/mL for AL 1064. This indirect comparison showed that, following four administrations, Ari 2MRTU 960 and AL 1064 delivered mean aripiprazole plasma concentrations that remained above the minimum therapeutic concentration of aripiprazole over the 2-month dosing interval.