Manic Relapse Research Articles

Psychiatrist and Psychiatric Pharmacists Beliefs and Preferences for Atypical Antipsychotic Treatments in Patients With Schizophrenia and Bipolar Disorders

Background: Selection of schizophrenia or bipolar disorder treatments is complicated by treatment-effect heterogeneity. Objectives: This study assessed how clinicians’ beliefs and health system/ insurace policies impact choice of atypical antipsychotic agent in schizophrenia and bipolar disorder. Methods: A cross-sectional survey was conducted of members of the American College of Clinical Pharmacy and College of Psychiatric & Neurologic Pharmacists. Beliefs regarding atypical antipsychotic effectiveness and safety, impact of comorbidity on drug selection, and factors influencing atypical antipsychotic therapy selection were assessed. Results: Twenty-four psychiatric pharmacists and 18 psychiatrists participated. Mean age was 39.6 years, 57.1% were female. Most clinicians (64.3%) believed medication effectiveness and safety equally important, while 26.2% believed safety and 9.4% believed effectiveness more important. The most important medication properties for schizophrenia were reducing positive symptoms (92.7%) and hospitalizations (87.8%) and for bipolar disorder were reducing manic episodes (87.8%), episode relapse (53.7%), and hospitalizations (53.7%). Agranulocytosis (78.1%), arrhythmias (70.7%), and extrapyramidal side effects (68.3%) were most concerning. Restrictions affected antipsychotic choice at 80.5% of sites and were believed to affect medication adherence (55.0%) and outcomes (53.4%). Conclusion: Efficacy and safety were considered equally important when choosing atypical antipsychotics. Formulary restrictions were perceived as impacting treatment choice and outcomes.

Timing of onset of lithium relapse prevention in bipolar disorder: evidence from randomised trials.

Lithium is widely prescribed, but the timing of key effects remains uncertain. The timing of onset of its relapse prevention effects is clarified by placebo-controlled randomised trials (3 studies, n = 1120). Lithium reduced relapse into any mood episode over the first 2 weeks of treatment (hazard ratio 0.40, 95% CI 0.16-0.97). Fewer manic relapses were evident within the first 4 weeks, however, early effects on depressive relapse were not demonstrated. There is an early onset of lithium relapse prevention effects in bipolar disorder, particularly against manic relapse. Full effects against depressive relapse may develop over a longer period.Declaration of interestM.J.T. reports personal fees from Sunovion, Otsuka, Lundbeck, outside the submitted work.

Attempting to stop antipsychotic medication: success, supports, and efforts to cope.

To explore supports and coping strategies used during attempts to discontinue antipsychotic medication and test for associations with success. 144 people who were taking or had taken antipsychotics completed The Experiences of Antipsychotic Medication Survey. Among them, 105 people had made at least one discontinuation attempt and answered a series of questions about their most recent attempt to stop. Content analysis and Chi-square tests of independence were used to categorise the data and explore associations. Success was defined as stopping all AM use irrespective of the duration of the medication-free period or whether relapse occurred, which were explored separately. Among the 105 people who had attempted discontinuation, 61.9% described unwanted withdrawal effects and 27.6% of the group described psychotic or manic relapse during the withdrawal period. Within this group 55% described successfully stopping all AM for varying lengths of time, half reported no current use, and half described having some form of professional, family, friend, and/or service user or peer support for their attempt. Having support was positively associated with success and negatively associated with both current use, and relapse during withdrawal. A range of coping efforts were described, but having coping strategies failed to show significant associations with any of the dependent variables explored. Among those who described successfully stopping, some described returning to AM for short periods when needed, while others reported managing well with alternative methods alone. Findings cannot be readily generalised due to sampling constraints, but results suggest a wide range of supports and coping strategies may be used when attempting to discontinue antipsychotics. Many people may attempt to discontinue antipsychotics without any support. Those who have support for their attempts may be significantly less likely to relapse during withdrawal and more likely to succeed in their attempt. There is a pressing need for further research in this area.

Efficacy of Group Cognitive-behavioral Therapy in Maintenance Treatment and Relapse Prevention for Bipolar Adolescents.

Background:Despite conducting wide-ranging of pharmacotherapy for bipolar adolescents, many of them are showing a deficit in functioning with high relapse rate. The aim of the current study was to develop a manual and investigate the efficacy of group cognitive–behavioral therapy (G-CBT) for female bipolar adolescents.Materials and Methods:During the first qualitative phase of a mixed-methods study, a manual of G-CBT was developed. Then, 32 female bipolar adolescents aged 12–19 years old, receiving usual maintenance medications (UMM), were selected. Participants were randomized to the control (UMM) and intervention group (5, 2 h weekly sessions based on G-CBT manual with UMM). The parents in intervention group participated in three parallel sessions. All participants filled the following questionnaires before 1, 3, and 6 months after the initiation of the study: Young Mania Rating Scale, Children Depression Inventory and Global Assessment of Functioning. The results were analyzed using SPSS 21 software. The concurrent qualitative phase was analyzed through thematic analysis.Results:The results showed no significant differences in all questionnaires’ scores through intervention and follow-up sessions (P > 0.05). However, using cutoff point of CDI, G-CBT was effective for intervention group (relapse rate: 25% vs. 44.4%). Two themes were extracted from the second qualitative phase: emotion recognition and emotion regulation, especially in anger control.Conclusions:The results showed that the addition of G-CBT to UMM leads to decrease in the depressive scores but has no effect on manic symptoms and relapse rate.

Do not treat the numbers: lithium toxicity

We describe the case of a 62-year-old man with a history of bipolar disorder, previously stable on lithium for over 20 years, who presented with a manic relapse and signs...

Modifiable and non-modifiable factors associated with functional impairment during the inter-episodic periods of bipolar disorder.

The chronic, long-term evolution of bipolar disorder (BD) requires a careful clinical characterization with prognostic implications in terms of symptom and functional control. The OPTHYMUM multicenter study was conducted in France with the objective of evaluating residual symptoms on overall functioning of BD patients during inter-episodic period. The aims of the present study were to identify the potentially modifiable (e.g., treatable) and non-modifiable variables associated with functional impairment during the inter-episodic periods of BD. Sample was divided into two groups according to level of functioning (adequate vs. impaired), based on the FAST scale total score. FAST cut-off for functional impairment is a score >11. The two subgroups were compared as per sociodemographic and clinical variables with standard univariate analyses, and a logistic regression model was created. The model as a whole contained independent non-modifiable factors (age, gender, BD type, illness duration) and modifiable factors (illness severity, predominant polarity, depressive and manic residual symptoms, comorbidities). The final model was statistically significant (χ 2=53.89, df=5, p<0.001). Modifiable factors most strongly associated with functional impairment were manic predominant polarity (OR=1.79, CI 95% 1.09-2.96, p=0.022), residual depressive symptoms (OR=1.30, CI 95% 1.18-1.43, p<0.001) and illness severity (OR=1.24, CI 95% 1.01-1.52, p=0.037), whilst non-modifiable factor was illness duration (OR=1.03, CI 95% 1.01-1.05, p=0.017). Despite intrinsic and non-modifiable illness characteristics, a clinical-wise choice of treatment may help to improve control of manic relapses. Potential improvement of residual depressive symptoms may alleviate the functional burden associated with bipolar disorder.

Bipolar disorder: an overview

Bipolar disorder (BD) is a chronic disorder characterised by abnormal mood changes and fluctuation in energy levels. The disease is characterised by a depressive episode, which can last up to a few months, and include low energy levels, hypersomnia, cognitive impairments, decreased sexual desire, carbohydrate craving, and weight gain. Conversely, bipolar disorder also has a stage of exhilaration and excitement, which can be classified as a manic episode. The typical presentation of these episodes of mania includes high energy hallucinations and delusions, sleep deprivation, fast speech and a constant need to be active. Risk factors that contribute to development of BD include the use of cannabis, influenza during the third trimester of pregnancy, as well as smoking during pregnancy, the use of cocaine, opioids, tranquilisers, stimulants and sedatives during pregnancy, and regular substance use during a period of a year. Parental loss before the age of five, war trauma and stress, as well as traumatic head injury may influence the condition.&#x0D; &#x0D; Clinical criteria are the mainstay of diagnosis of BD. Differentiating features, which were found to be related to BD, include early age of onset, family history, atypical features and mixed symptoms. Screening tools like the Mood Disorder Questionnaire (MDQ) and Hypomania Checklist (HCL-32) have shown the ability to differentiate BD from major depressive disorder (MDD). &#x0D; &#x0D; Treatment differs between the different phases of BD, but lithium can be considered as initial monotherapy, since it is effective against manic, depressive and mixed relapses, and has shown better evidence for prevention of new episodes. It is also associated with a reduced risk of suicide and self-harm in BD patients.

Psychosocial therapies for the adjunctive treatment of bipolar disorder in adults: network meta-analysis.

BackgroundFew trials have compared psychosocial therapies for people with bipolar affective disorder, and conventional meta-analyses provided limited comparisons between therapies.AimsTo combine evidence for the efficacy of psychosocial interventions used as adjunctive treatment of bipolar disorder in adults, using network meta-analysis (NMA).MethodSystematic review identified studies and NMA was used to pool data on relapse to mania or depression, medication adherence, and symptom scales for mania, depression and Global Assessment of Functioning (GAF).ResultsCarer-focused interventions significantly reduced the risk of depressive or manic relapse. Psychoeducation alone and in combination with cognitive-behavioural therapy (CBT) significantly reduced medication non-adherence. Psychoeducation plus CBT significantly reduced manic symptoms and increased GAF. No intervention was associated with a significant reduction in depression symptom scale scores.ConclusionsOnly interventions for family members affected relapse rates. Psychoeducation plus CBT reduced medication non-adherence, improved mania symptoms and GAF. Novel methods for addressing depressive symptoms are required.

Psychiatric and physical comorbidities and their impact on the course of bipolar disorder: A prospective, naturalistic 4-year follow-up study.

The aim of the present study was to increase the available evidence on how physical and psychiatric comorbidities influence the long-term outcome in bipolar I and II disorder. We examined the prevalence of comorbid physical (metabolic, cardiovascular, thyroid, and neurological) diseases and psychiatric (neurotic, stress-related, somatoform, and personality) disorders and their impact on the risk of relapse in bipolar disorder. A total of 284 consecutively admitted patients with ICD-10 bipolar I (n=161) and II (n=123) disorder were followed up naturalistically over a period of 4years. Globally, 22.0% patients had metabolic, 18.8% cardiovascular, 18.8% thyroid, and 7.6% neurological diseases; 15.5% had neurotic, stress-related, and somatoform disorders; 12.0% had personality disorders; and 52.9% had nicotine dependence. We did not find any effect of comorbid metabolic, cardiovascular or neurological diseases or psychiatric disorders on the relapse risk. However, the presence of thyroid diseases, and especially hypothyroidism, was associated with an increased risk of manic relapse in bipolar disorder I (thyroid disease: hazard ratio [HR]=2.7; P=.003; hypothyroidism: HR=3.7;, P<.001). Among patients with hypothyroidism, higher blood levels of baseline thyroid-stimulating hormone (bTSH) were also associated with an increased risk of manic relapse (HR=1.07 per milli-international units per liter; P=.011), whereas blood levels of free triiodothyronine (fT3 ) or free thyroxine (fT4 ) were not found to have an influence. Our data underline the negative long-term impact of thyroid diseases, and especially hypothyroidism with high blood levels of bTSH, on bipolar disorder with more manic episodes, and the importance of its detection and treatment.

Isolated rhabdomyolysis caused by olanzapine: About a clinical case

IntroductionAtypical anti-psychotics are increasingly prescribed, given their tolerance. Among these anti-psychotic olanzapine, known for its adverse metabolic effects. By against an adverse event type rhabdomyolysis with olanzapine appears uncommon (&lt;1%) and few clinical cases have been reported in the literature.AimThe aim of our study is to illustrate with a clinical case the occurrence of an isolated rhabdomyolysis with olanzapine.Materiel and methodStarting from the study of the case of a patient with rhabdomyolysis with olanzapine we studied the literature data. Clinical vignette: it is about a patient aged 25 followed for bipolar disorder type I. He responded to the association olanzapine and valproic acid then to valproic acid only. His last hospitalization for manic relapse dating to September 9, 2015 occurred in a context of treatment discontinuation. Upon admission the patient underwent an oral treatment based olanzapine and valproic acid. A dosage of creatine phosphokinase (CPK) done systematically, on September 11 showed high levels of (CPK) to 973 (U/L) without clinical signs of neuroleptic malignant syndrome. The electrocardiogram and biological tests results were normal. Other etiologies can lead to elevated (CPK) were eliminated. The persistent elevation of CPK motivated the arrest of olanzapine. The evolution was marked by a return to normal CPK rates after 15 days. The olanzapine was replaced by haloperidol and vaproic acid maintained. The pharmacovigilance investigation conclude to the accountability of olanzapine in this rhabdomyolysis.ConclusionSecond generation, anti-psychotics are known for their better tolerance compared to conventional antipsychotics. However, they are not devoid of side effects.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Doping control analysis of lithium in horse urine and plasma by inductively coupled plasma mass spectrometry.

Lithium salts are commonly prescribed to treat bipolar disorder in humans. They are effective for the treatment of acute mania and the prophylaxis of manic relapses through long-term use. Although there is no reported legitimate therapeutic use of lithium in horses, its potential mood-stabilizing effect, low cost, and ready availability make lithium salt a potential agent of abuse in equine sports, especially for equestrian competition horses. Lithium can be found in soil, plants, and water, as such it is naturally present in the equine body, thus a threshold is necessary to control its misuse in horses. This paper describes the validation of quantification methods for lithium in equine urine and plasma using inductively coupled plasma mass spectrometry (ICP-MS). Based on a population study of lithium in horse urine and an administration study using a single oral dose of lithium chloride (100mg) to mimic the daily lithium intake from a diet rich in lithium, a urinary threshold of 5μg/mL was proposed. Applying this urinary threshold to two other administration studies (a single oral dose of 65g of lithium chloride, and a single intravenous dose of 2.54g of lithium chloride), excessive lithium in urine could be detected for 8days and 2.5days respectively. The concentrations of lithium in plasma following these three lithium chloride administration trials were also studied. Copyright © 2017 John Wiley & Sons, Ltd.

Neuropsychiatric Complexities in the HIV Patient – Clinical Challenges beyond Neurocognitive Disorders

Objective: To illustrate clinical challenges, explore existing literature and identify knowledge gaps in the management of neuropsychiatric issues beyond neurocognitive disorders in HIV patients. Methods: Three case vignettes from a consultation-liaison psychiatry setting in a general hospital were collated and summarised into a case series. Clinical questions were identified from each vignette and pertinent literature reviewed to aid a further discussion of management issues. Results: The first case vignette discusses the potential of a multi-dimensional approach to the formulation of a HIV patient with emergent psychiatric and cognitive symptoms. In the second, pharmacological treatment of a HIV patient with a severe manic relapse of Bipolar 1 Disorder and active TB disease is discussed. Lastly, the collective effects of severe Traumatic Brain Injury (TBI) and HIV infection superimposed on that of an ageing brain are described. Iatrogenic risks of polypharmacy in an elderly HIV patient are further explored. Conclusion: The practical aspects of clinical challenges regarding the management of HIV patients are multi-fold and most apparent in a real-world setting. Existing literature does not yet adequately address the diagnostic dilemmas and pharmacological complexities faced. The management of other neuropsychiatric manifestations in a HIV patient remains a crucial field to be explored.

Association of family history of bipolar disorder with risk of violence in inpatient mania: a cohort study

Background Evidence suggests that a positive family history of bipolar affective disorder is associated with response to lithium and the course of the illness, in people suffering from this disorder. This may indicate a subgroup of patients with unique characteristics and treatment responses. Aims To explore associations between a positive family history of bipolar disorder and the risk of violence, in patients hospitalized for treatment of mania. Methods Adults receiving inpatient treatment for a manic relapse of bipolar affective disorder, at two tertiary care hospitals in Kandy, Sri Lanka were studied as a cohort. For each participant with a positive family history of bipolar disorder, an age and gender matched adult, also suffering from a manic relapse of bipolar affective disorder but without a family history, was included as a control. A second researcher, who was blind to the participants’ family history, assessed the risk of violence among all participants, at baseline, and at weekly intervals thereafter until discharge, using the historical clinical risk management Scale 20 (HCR-20). Results A total of 148 participants were included, with 74 each in the study arm and control arm respectively. Of all participants, 57% were females. Significantly higher rates of unemployment, harmful use of alcohol and absence of confiding relationships were found in participants with a positive family history; they also had a significantly higher mean average HCR-20 scores compared to controls. Conclusion A positive family history of bipolar affective disorder was associated with a higher risk of violence during hospitalization for a manic relapse, as indicated by the mean average HCR-20 scores. A positive family history may be a potential identifier of those at a higher risk of violence in bipolar mania.

Prophylactic efficacy of lithium, valproic acid, and carbamazepine in the maintenance phase of bipolar disorder: a naturalistic study.

Mood stabilizers are used clinically for the management of bipolar disorder. Prophylactic therapy with mood stabilizers is the primary treatment for preventing depressive and manic relapses in bipolar patients once they are stabilized. In this study, we examined the relative efficacy of the three most commonly used mood-stabilizing agents: lithium (Li), valproic acid (VPA), and carbamazepine (CBZ), in preventing relapse episodes. A total of 225 patients with bipolar disorder were included in the present analysis. Patients taking Li, VPA, or CBZ were followed up for up to 124 months, until suffering a manic, mixed, or depressive episode (relapse), or until the end of the study/study termination (no relapse), whichever came first. The median unadjusted survival time was 36 months for patients taking VPA, 42 months for patients taking CBZ, and 81 months for patients taking Li. These results indicate that patients stayed longer on Li, suggesting that it might have been better tolerated than either CBZ or VPA. χ-Analysis showed that patients taking Li were significantly less likely to experience relapse during the observational period than patients taking either VPA or CBZ (P<0.05). A Cox regression model showed that the hazard of experiencing relapse was significantly predicted by the total number of depressive (P=0.007) and manic symptoms (P=0.02) assessed before the observation period. In addition, after controlling for symptom covariates, the hazard of experiencing relapse was 1.66 times (95% confidence interval 1.03-2.67) or 66% higher for patients taking VPA compared with patients taking Li (P=0.037). Although the hazard of experiencing relapse was higher for patients taking CBZ compared with those taking Li, the risk was not elevated by a significant amount. Notwithstanding the limitations of the naturalistic design of this study, the differences in relapse prevention and survival time observed in these medications show Li fairing relatively better in prophylactic therapy.

Multifractal dynamics of activity data in bipolar disorder: Towards automated early warning of manic relapse

Multifractal dynamics of activity data in bipolar disorder: Towards automated early warning of manic relapse

Measuring patient outcomes and making the transition from acute to maintenance treatment for bipolar depression.

Patients with bipolar disorder require diligent management involving psychoeducation, a strong therapeutic alliance, and ongoing monitoring with rating scales to achieve the best outcomes. Clinicians should monitor symptom response, functioning, and quality of life to determine if treatment needs to be be adjusted. Assessing adverse effects must be done regularly to improve treatment adherence. Because effective acute phase treatments are often continued in maintenance treatment, clinicians must find the right balance of efficacy and tolerability for long-term success. The FDA has approved 7 agents for maintenance treatment of bipolar disorder. Because of the high risk of recurrent depressive episodes, clinicians should be aware of which agents are more effective for reducing manic or depressive relapses.

Estimated medical cost reductions for paliperidone palmitate vs placebo in a randomized, double-blind relapse-prevention trial of patients with schizoaffective disorder

Objective:The objective of this economic model was to estimate the difference in medical costs among patients treated with paliperidone palmitate once-monthly injectable antipsychotic (PP1M) vs placebo, based on clinical event rates reported in the 15-month randomized, double-blind, placebo-controlled, parallel-group study of paliperidone palmitate evaluating time to relapse in subjects with schizoaffective disorder.Research design and methods:Rates of psychotic, depressive, and/or manic relapses and serious and non-serious treatment-emergent adverse events (TEAEs) were obtained from the long-term paliperidone palmitate vs placebo relapse prevention study. The total annual medical cost for a relapse from a US payer perspective was obtained from published literature and the costs for serious and non-serious TEAEs were based on Common Procedure Terminology codes. Total annual medical cost differences for patients treated with PP1M vs placebo were then estimated. Additionally, one-way and Monte Carlo sensitivity analyses were conducted.Results:Lower rates of relapse (−18.3%) and serious TEAEs (−3.9%) were associated with use of PP1M vs placebo as reported in the long-term paliperidone palmitate vs placebo relapse prevention study. As a result of the reduction in these clinical event rates, the total annual medical cost was reduced by $7140 per patient treated with PP1M vs placebo. One-way sensitivity analysis showed that variations in relapse rates had the greatest impact on the estimated medical cost differences (range: −$9786, −$4670). Of the 10,000 random cycles of Monte Carlo simulations, 100% showed a medical cost difference <$0 (reduction) for patients using PPIM vs placebo. The average total annual medical differences per patient were −$8321 for PP1M monotherapy and −$6031 for PPIM adjunctive therapy.Conclusions:Use of PP1M for treatment of patients with schizoaffective disorder was associated with a significantly lower rate of relapse and a reduction in medical costs compared to placebo. Further evaluation in the real-world setting is warranted.

The real world cost and health resource utilization associated to manic episodes: The MANACOR study

IntroductionBipolar disorder is a relapsing-remitting condition affecting approximately 1–2% of the population. Even when the treatments available are effective, relapses are still very frequent. Therefore, the burden and cost associated to every new episode of the disorder have relevant implications in public health. The main objective of this study was to estimate the associated health resource consumption and direct costs of manic episodes in a real world clinical setting, taking into consideration clinical variables. MethodsBipolar I disorder patients who recently presented an acute manic episode based on DSM-IV criteria were consecutively included. Sociodemographic variables were retrospectively collected and during the 6 following months clinical variables were prospectively assessed (YMRS,HDRS-17,FAST and CGI-BP-M). The health resource consumption and associate cost were estimated based on hospitalization days, pharmacological treatment, emergency department and outpatient consultations. ResultsOne hundred and sixty-nine patients from 4 different university hospitals in Catalonia (Spain) were included. The mean direct cost of the manic episodes was €4771. 77% (€3651) was attributable to hospitalization costs while 14% (€684) was related to pharmacological treatment, 8% (€386) to outpatient visits and only 1% (€50) to emergency room visits. The hospitalization days were the main cost driver. An initial FAST score >41 significantly predicted a higher direct cost. ConclusionsOur results show the high cost and burden associated with BD and the need to design more cost-efficient strategies in the prevention and management of manic relapses in order to avoid hospital admissions. Poor baseline functioning predicted high costs, indicating the importance of functional assessment in bipolar disorder.

The real world cost and health resource utilization associated to manic episodes: The MANACOR study.

Bipolar disorder is a relapsing-remitting condition affecting approximately 1-2% of the population. Even when the treatments available are effective, relapses are still very frequent. Therefore, the burden and cost associated to every new episode of the disorder have relevant implications in public health. The main objective of this study was to estimate the associated health resource consumption and direct costs of manic episodes in a real world clinical setting, taking into consideration clinical variables. Bipolar I disorder patients who recently presented an acute manic episode based on DSM-IV criteria were consecutively included. Sociodemographic variables were retrospectively collected and during the 6 following months clinical variables were prospectively assessed (YMRS,HDRS-17,FAST and CGI-BP-M). The health resource consumption and associate cost were estimated based on hospitalization days, pharmacological treatment, emergency department and outpatient consultations. One hundred sixty-nine patients patients from 4 different university hospitals in Catalonia (Spain) were included. The mean direct cost of the manic episodes was €4,771. The 77% (€3,651) was attributable to hospitalization costs while 14% (€684) was related to pharmacological treatment, 8% (€386) to outpatient visits and only 1% (€50) to emergency room visits. The hospitalization days were the main cost driver. An initial FAST score>41 significantly predicted a higher direct cost. Our results show the high cost and burden associated with BD and the need to design more cost-efficient strategies in the prevention and management of manic relapses in order to avoid hospital admissions. Poor baseline functioning predicted high costs, indicating the importance of functional assessment in bipolar disorder.

Bipolar Disorder and Male Infertility: Which is the Role of Valproic Acid? a Case Report

The Valproic Acid (VPA) is an alternative choice in the treatment of bipolar disorders, because it provides a synergistic mood-stabilisingband antipsychotic activity. Many side effects are well-known, (hepatotoxicity, hyperammonemic encephalopathy, metabolic and endocrine adverse events). The worldwide increasing rate of infertility induced many researchers to focus also on effects on female reproductive abnormalities, but male infertility was not followed by a similar number of studies. In our case report, we describe a case of male infertility probably related to valproate (VPA) exposure. A 51-year-old man suffering from bipolar disorder came to our attention during a manic relapse, since he had discontinued any therapy (Olanzapine 300 mg/die and Haloperidole 5 mg/die) because of weight gain and stigma in his social life. Subsequently, we prescribed Paliperidone 3 mg/die and VPA 900 mg/die and he had a rapid recover. After few months he showed us an infertility evaluation revealing a sperm count of 10,000,000/ml, but no motile sperm (100%), 90% with abnormal structure, in contrast with a 15 months older sperm exam, displaying 35% motile sperm. A hormonal evaluation of prolactine showed slightly higher rate (19,31 ng/ml), not enough to explain such laboratory results. Eventually, we decided to discontinue VPA and now we are waiting for further exams. Even if rare, a direct effect of VPA on spermatic structure and function could be not so unusual as thought; despite this, we cannot exclude a role of paliperidone in our patient’s fertility reduction, thus suggesting that further studies are needed.