Risk Factors Associated With Antidepressant Exposure and History of Antidepressant-Induced Mania in Bipolar Disorder.

OBJECTIVE: Despite their widespread use in bipolar disorder, there is controversy surrounding the inclusion of antidepressant medications in the disorder's management. We sought to identify which demographic, socioeconomic, and clinical factors are associated with antidepressant exposure in bipolar disorder and which bipolar disorder patients are most likely to report a history of antidepressant-induced mania (AIM) when exposed to antidepressants. METHODS: Our study included subjects with bipolar I disorder (n = 309), bipolar II disorder (n = 66), and bipolar disorder not otherwise specified (n = 27) and schizoaffective disorder, bipolar type (n = 14), from a longitudinal, community-based study. Subjects were evaluated using the Diagnostic Interview for Genetic Studies, modified for DSM-IV criteria. We applied multivariate logistical regression modeling to investigate which factors contribute to antidepressant exposure in bipolar disorder patients. We also used a logistic regression modeling approach to determine which clinical factors in bipolar disorder patients are associated with a history of AIM. Data were gathered from February 2006 through December 2010. RESULTS: Our results suggest that the risk factors most strongly associated with antidepressant exposure are female sex (OR = 2.73, P = .005), older age (OR = 1.03, P = .04), greater chronicity of illness (OR = 2.29, P = .04), and, to a lesser extent, white race (OR = 0.44, P = .051). Factors associated with reduced antidepressant exposure include history of affective psychosis (OR = 0.36, P = .01) and a greater number of previous manic episodes (OR = 0.98, P = .03). In subjects who reported a history of AIM, regression analysis revealed that the only statistically significant factor associated with AIM history was female sex (OR = 3.74, P = .02). CONCLUSIONS: These data suggest that there are certain identifiable factors associated with antidepressant exposure in bipolar disorder patients, and some of these, specifically female sex, are also associated with a history of AIM. These data may be useful in designing prospective trials to identify interventions that can reduce the risk of this adverse outcome.

Cannabis induced psychosis and subsequent psychiatric disorders.

INTRODUCTION: Long term change in diagnosis of patients having Cannabis induced psychosis (CIP) at the index evaluation is well recognised. Some patients are known to achieve complete remission while others go on to develop independent schizophrenia or mood disorders. AIMS: To study the long-term course of CIP and factors influencing it. METHOD: Patients diagnosed as CIP (ICD 10: F12.5), admitted at NIMHANS, a tertiary neuropsychiatry centre at Bangalore, over the past 10 years were identified from medical records. 200 case records were identified and screened in detail. 57 met inclusion criteria and 35 patients could be followed up. Mean follow up duration was 5.75 years. RESULTS: Patients who completely abstained from cannabis after the 1st episode had no relapse of psychiatric illness. They showed marked improvement in socio-occupational functioning as well. All those who relapsed to cannabis use had a recurrence of illness. Half the patients with predominantly non-affective psychosis progressed to an independent psychiatric disorder; while only 7.7% patients with predominantly affective psychosis developed an independent disorder (p=0.01). Besides this, early onset of cannabis use (≤18years), younger age at onset of 1st episode, positive family history of psychiatric illness, being unmarried and lower socio-economic status were associated with poor prognosis. Abstinence later in the course of illness did not improve outcome significantly. CONCLUSION: Abstaining from cannabis early in the course of illness is critical for good recovery. The course of CIP is variable and categorising CIP into affective vs. non-affective psychosis can be useful in clinical practice.

Donepezil-associated manic episode with psychotic features: a case report and review of the literature.

OBJECTIVE: Reports of manic episodes associated with the use of cholinesterase inhibitors (including donepezil) are limited. Despite the previous notion of procholinergic drugs potentially inducing depression, the contemporary evidence for cholinesterase inhibitors appears to also indicate a trend for elevated mood (in patients with or without a history of depressive disorder). METHOD: Case report. RESULTS: The authors report a case of a manic episode with psychotic features associated with the up-titration of donepezil in a patient with Alzheimer's disease and a distant history of major depression but without a preexisting bipolar disorder. CONCLUSION: Pathophysiology of donepezil-induced mania appears to contradict the traditional cholinergic-adrenergic hypothesis. Donepezil-associated mania should be suspected after donepezil initiation/dose up-titration when correlated to new onset of mania. Donepezil should be used more cautiously in patients with current or previous mood episodes or in those who are otherwise at high risk for manic episodes (e.g., cerebrovascular disease). Although this requires further investigation in different patient populations, there may be subtypes of older patients with neurocognitive disorders who are particularly vulnerable to activation effects of cholinesterase inhibitors.

Manía inducida por bebidas energéticas con alto contenido de cafeína / Mania induced by high content caffeinated energy drinks

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Relación entre tabaco y sintomatología psicótica en paciente tratado con olanzapina oral. A propósito de un caso / Relationship between smoking and psychotic symptoms in a patient treated with oral olanzapine. A case report

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Psychosis following chloroquine ingestion: a 10-year comparative study from a malaria-hyperendemic district of India.

OBJECTIVES: Serious adverse effects such as acute psychoses have been reported following treatment with chloroquine. Chloroquine can cause cell death, including neurons. We aimed to identify the most frequent type of psychiatric manifestation and symptomatological characteristics of psychosis following chloroquine ingestion (PFC). METHOD: Out of a total of 4471 randomly selected recent-onset psychosis patients, 3610 consecutive patients who had responded to standard treatment were screened for entry in the study. We compared background clinicodemographic profile information and psychopathology of 51 PFC patients, who were either drug free or drug naive, to 51 brief psychotic disorder (BPD) patients who were matched in terms of age, sex and education. Only those patients who remitted within 8 weeks (PFC patients) or 4 weeks (BPD patients) were included. Cranial computed tomography, electroencephalography and lumbar puncture of the entire experimental group were normal, and none had Mini Mental Status Examination score <22. Group difference and correlational statistics (parametric and nonparametric) have been used to test the hypotheses and explain the results. RESULTS: The most common (76.2%) type of psychiatric disturbance in PCF group was mood disorder (mixed episode) accompanied by predominant irritability with little blunting of affect. PFC patients characteristically had prominent positive symptoms with visual hallucination and derealization experiences. They were more restless, agitated and anxious and had more disturbed thought content and orientation, but better preserved insight. There was no linear relationship between the amount of chloroquine consumed and the severity of psychosis. CONCLUSION: Considering the large number of patients still receiving chloroquine especially in developing countries, this study has been presented to draw attention of the psychiatrists and other health professionals to the hazardous effect of chloroquine on mental health.

Association between environmental exposure to pesticides and neurodegenerative diseases.

Preliminary studies have shown associations between chronic pesticide exposure in occupational settings and neurological disorders. However, data on the effects of long-term non-occupational exposures are too sparse to allow any conclusions. This study examines the influence of environmental pesticide exposure on a number of neuropsychiatric conditions and discusses their underlying pathologic mechanisms. An ecological study was conducted using averaged prevalence rates of Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebral degeneration, polyneuropathies, affective psychosis and suicide attempts in selected Andalusian health districts categorized into areas of high and low environmental pesticide exposure based on the number of hectares devoted to intensive agriculture and pesticide sales per capita. A total of 17,429 cases were collected from computerized hospital records (minimum dataset) between 1998 and 2005. Prevalence rates and the risk of having Alzheimer's disease, Parkinson's disease, multiple sclerosis and suicide were significantly higher in districts with greater pesticide use as compared to those with lower pesticide use. The multivariate analyses showed that the population living in areas with high pesticide use had an increased risk for Alzheimer's disease and suicide attempts and that males living in these areas had increased risks for polyneuropathies, affective disorders and suicide attempts. In conclusion, this study supports and extends previous findings and provides an indication that environmental exposure to pesticides may affect the human health by increasing the incidence of certain neurological disorders at the level of the general population.

Drugs with anticholinergic properties: cognitive and neuropsychiatric side-effects in elderly patients.

Drug consumption in older people is usually high and many prescribed medications have unsuspected anticholinergic (ACH) (Table 1) properties. Drug induced ACH side-effects are particularly severe in aging brain and even more in demented patients. This review will focus on the association between ACH drug intake and the risk of developing central nervous system side-effects in elderly people. The threat of developing cognitive impairment, psychosis and delirium will be particularly analyzed.

Risk of psychosis exacerbation by tricyclic antidepressants in unipolar Major Depressive Disorder with psychotic features.

BACKGROUND: We conducted a systematic review of the published trials in unipolar Major Depressive Disorder with psychotic features (MDDP) to examine the risk of psychosis exacerbation by antidepressants. METHODS: We searched Medline, Cochrane Central Register of Controlled Trials, PsychINFO, and EMBASE for English language, controlled, open or retrospective acute antidepressant and/or antipsychotic treatment studies of unipolar MDDP. Studies without a clear delineation of treatment course or between bipolar disorder and unipolar MDDP were excluded. We evaluated studies for the number of subjects with psychosis exacerbation, and contacted the corresponding author for ambiguous cases. Studies in which we were unable to determine rates of psychosis exacerbation were excluded. Psychosis exacerbation was determined on a categorical basis, and analyzed with Fisher's exact test, a modified Wald confidence interval and odds ratio. RESULTS: 20 studies meeting criteria provided sufficient adverse event reporting for inclusion. 15 of 177 subjects (8.5%) on antidepressant monotherapy had a psychosis exacerbation, 8 of whom were on tricyclics. 2 of 129 subjects on either antipsychotic or combination treatment had a psychosis exacerbation. Tricyclic monotherapy was significantly more likely to be temporally associated with psychosis exacerbation (p=0.007). LIMITATIONS: Limitations include the small number of placebo-controlled trials, and numerous studies in which the relevant information was missing. Additionally, most trials were designed as treatment outcome studies, and not to determine the rate of psychosis exacerbation. CONCLUSIONS: Although rare, the present study indicates that tricyclic monotherapy may be temporally associated with an exacerbation of psychotic symptoms in patients with unipolar MDDP, potentially worsening prognosis.

A randomized controlled trial of venlafaxine ER and paroxetine in the treatment of outpatients with panic disorder.

RATIONALE: Few randomized, placebo-controlled trials have evaluated the comparative efficacy and tolerability of more than one pharmacological agent for panic disorder. OBJECTIVES: The primary objective of this study was to compare the efficacy and tolerability of venlafaxine extended release (ER) with placebo in treating panic disorder. Secondary objectives included comparing paroxetine with venlafaxine ER and placebo. METHODS: Outpatients aged > or =18 years (placebo, n = 157; venlafaxine ER 75 mg, n = 156; venlafaxine ER 225 mg, n = 160; paroxetine, n = 151), with a primary diagnosis of panic disorder (+/-agoraphobia) based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for > or =3 months were randomly assigned to receive venlafaxine ER (titrated to 75 mg/day or 225 mg/day), paroxetine (titrated to 40 mg/day), or placebo for 12 weeks. The primary efficacy measure was the percentage of patients free of full-symptom panic attacks (> or = four symptoms) at endpoint. Key secondary outcomes included the Panic Disorder Severity Scale (PDSS) mean score change and response. RESULTS: At endpoint, all active treatment groups showed a significantly (P < 0.01) greater proportion of patients free of full-symptom panic attacks, compared with placebo, and were superior (P < 0.05) on most secondary measures. The venlafaxine ER 225 mg group had significantly (P < 0.05) greater mean PDSS score improvement than the paroxetine group (-12.58 vs -11.87) and a significantly higher proportion of patients free of full symptom panic attacks (70.0 vs 58.3%). Both drugs were generally well tolerated. CONCLUSION: Venlafaxine ER 75 mg/days and 225 mg/days and paroxetine 40 mg/day were both well tolerated and effective for short-term treatment of panic disorder.

Comorbidity between substance use disorders and psychiatric conditions.

AIM: To review information relevant to the question of whether substance-induced mental disorders exist and their implications. DESIGN AND METHOD: This paper utilized a systematic review of manuscripts published in the English language since approximately 1970 dealing with comorbid psychiatric and substance use disorders. FINDINGS: The results of any specific study depended on the definitions of comorbidity, the methods of operationalizing diagnostic criteria, the interview and protocol invoked several additional methodological issues. The results generally support the conclusion that substance use mental disorders exist, especially regarding stimulant or cannabinoid-induced psychoses, substance-induced mood disorders, as well as substance-induced anxiety conditions. CONCLUSIONS: The material reviewed indicates that induced disorders are prevalent enough to contribute significantly to rates of comorbidity between substance use disorders and psychiatric conditions, and that their recognition has important treatment implications. The current literature review underscores the heterogeneous nature of comorbidity.

Behavioural manifestations of anabolic steroid use.

The use of anabolic androgenic steroids (AAS) for gains in strength and muscle mass is relatively common among certain subpopulations, including athletes, bodybuilders, adolescents and young adults. Adverse physical effects associated with steroid abuse are well documented, but more recently, increased attention has been given to the adverse psychiatric effects of these compounds. Steroids may be used in oral, 17alpha-alkylated, or intramuscular, 17beta-esterified, preparations. Commonly, steroid users employ these agents at levels 10- to 100-fold in excess of therapeutic doses and use multiple steroids simultaneously, a practice known as 'stacking'. Significant psychiatric symptoms including aggression and violence, mania, and less frequently psychosis and suicide have been associated with steroid abuse. Long-term steroid abusers may develop symptoms of dependence and withdrawal on discontinuation of AAS. Treatment of AAS abusers should address both acute physical and behavioural symptoms as well as long-term abstinence and recovery. To date, limited information is available regarding specific pharmacological treatments for individuals recovering from steroid abuse. This paper reviews the published literature concerning the recognition and treatment of behavioural manifestations of AAS abuse.

Mefloquine increases the risk of serious psychiatric events during travel abroad: a nationwide case-control study in the Netherlands.

BACKGROUND: Psychiatric events during travel abroad account for a large percentage of medical repatriations arranged by insurance companies. Several risk factors have been proposed for such events, one of these being use of mefloquine. We investigated the risk of psychiatric events during use of mefloquine. METHOD: We performed a nationwide case control study using medical records from 4 large alarm centers in the Netherlands. Cases were patients contacting the alarm centers because of psychiatric events, according to International Code Primary Care code P (all psychiatric symptoms) or International Classification of Diseases, Ninth Edition, codes 290-319 (all psychiatric syndromes). To every case we matched up to 6 controls by alarm center, calendar time, and continent of travel. All controls had contacted the alarm centers because of nonpsychiatric medical reasons. Shortly after the anticipated day of return, cases and controls received a questionnaire regarding travel characteristics, gender, age, marital status, education, weight, height, general health, history of psychiatric diseases, use of medicines, smoking status, alcohol intake, coffee intake, and use of malaria prophylaxis. Dates of travel for the source population were between September 1, 1997, and June 1, 2000. RESULTS: The study population consisted of 111 cases and 453 controls. The risk of psychiatric events during the use of mefloquine was 3.5 (95% CI = 1.4 to 8.7). In females, the risk was strongly increased, with an odds ratio of 47.1 (95% CI = 3.8 to 578.6). Stratification for history of psychiatric diseases showed that the risk of psychiatric events during use of mefloquine in cases without a history of psychiatric diseases was 3.8 (95% CI = 1.4 to 10.1), whereas the risk in cases with a history of psychiatric diseases was 8.0 (95% CI = 1.8 to 35.8). CONCLUSION: The use of mefloquine is associated with an increased risk of psychiatric events in females and in patients with a history of psychiatric diseases.

Major depressive disorder with psychotic features induced by interferon-alpha treatment for hepatitis C in a polydrug abuser.

Infectious diseases, especially hepatitis C, are prevalent among drug abusers. Interferon-alpha (IFN-alpha) is the pharmacological treatment of choice for this condition. Patients being treated with IFN-alpha can be expected to experience such psychiatric side-effects as development of depression, mania, irritability, changes in personality, hallucinations or delirium. In addition, certain patients are considered to be at greater risk of developing neuropsychiatric side-effects. Individuals meeting the following criteria are particularly vulnerable: over 40 years of age; having central nervous system abnormalities; a previous neurological or psychiatric history; a past familial psychiatric history; use of narcotics or having alcohol or substance use disorders; being HIV-positive; coadministration of other cytokines; receiving high doses of IFN-alpha (> 6 million units). We report the case of a 29-year-old patient with chronic non-active hepatitis C, a previous psychiatric history of polydrug abuse (cannabis, heroin and illegal use of the psychotropic drug biperiden) and anxiety disorder. Two weeks after the initiation of IFN-alpha treatment, he developed fatigue, sleeplessness and persecutory delusions. The patient responded partially to the discontinuation of the IFN-alpha treatment. Due to the presence of three risk factors in this patient, he was considered to belong to the group of patients being 'at high risk' of developing neuropsychiatric side-effects. This is the first case report of major depressive disorder with psychotic features in such a 'high-risk patient'. This case report may prompt other research by showing the importance of the close monitoring, and the prevention of the progression of IFN-alpha-related psychiatric disorders in 'a high-risk patient'.

The risk of severe depression, psychosis or panic attacks with prophylactic antimalarials.

INTRODUCTION/OBJECTIVE: Experimental and observational studies have linked mefloquine use to an increased risk of developing neuropsychiatric adverse effects such as depression or psychoses. Most of these reports relied on interview-based information from travellers. We conducted a population-based observational study using a database of medical records to quantify and compare the risk of psychiatric disorders during or after use of mefloquine with the risk during use of proguanil and/or chloroquine, or doxycycline. STUDY DESIGN/METHODS: The study population was drawn from the large UK-based General Practice Research Database (GPRD). Subjects were aged from 17-79 years and were exposed to mefloquine, proguanil, chloroquine or doxycycline (or a combination of these drugs) at some time between 1990 and 1999. We performed a person-time and a nested case-control analysis to assess the risk of developing a first-time diagnosis of depression, psychosis or panic attack during or after use of these antimalarial drugs. RESULTS: Within the study population of 35 370 subjects (45.2% males), we identified 580 subjects with a first-time diagnosis of depression (n = 505), psychosis (n = 16) or panic attack (n = 57) and two subjects committed suicide. The incidence rates of first-time diagnoses of depression during current use of mefloquine, proguanil and/or chloroquine, or doxycycline, adjusted for age, gender and calendar year, were 6.9 (95% CI 4.5-10.6), 7.6 (95% CI 5.5-10.5) and 9.5 (95% CI 3.7-24.1)/1000 person-years, respectively. The incidence rates of psychosis or panic attacks during current mefloquine exposure were 1.0/1000 person-years (95% CI 0.3-2.9) and 3.0/1000 person-years (95% CI 1.6-5.7), respectively, approximately 2-fold higher (statistically nonsignificant) than during current use of proguanil and/or chloroquine, or doxycycline. The nested case-control analysis encompassed 505 cases with depression and 3026 controls, 16 cases with psychosis and 96 controls, and 57 cases with a panic attack and 342 controls. Current use of mefloquine was not associated with an elevated risk of developing depression. In a comparison between patients currently using mefloquine with all past users of antimalarials combined, the risk estimate was elevated for current users of mefloquine for both psychosis (odds ratio [OR] 8.0, 95% CI 1.0-62.7; p < 0.05) and panic attacks (OR 2.7, 95% CI 1.1-6.5; p < 0.05). CONCLUSION: The absolute risk of developing psychosis or panic attack appears low with all the antimalarials tested. No evidence was found in this large observational study that mefloquine use increased the risk of first-time diagnosis of depression when compared with the use of other antimalarials investigated in this study.