Journal of Psychopharmacology current issue

Prescribing antidepressants post Cipriani et al

Nutt, D. J — Thu, 05 Nov 2009 08:24:39 PST

Early onset anxiolytic efficacy after a single dose of pregabalin: double-blind, placebo- and active-comparator controlled evaluation using a dental anxiety model

Nutt, D., Mandel, F., Baldinetti, F. — Thu, 05 Nov 2009 08:24:39 PST

To evaluate acute onset of anxiolytic activity using a dental anxiety model, 89 patients were randomised to double-blind single dose pregabalin 150 mg, alprazolam 0.5 mg or placebo 4 h before a scheduled dental procedure. A Dental Anxiety Total score >12 (moderate-to-severe) without meeting Diagnostic and Statistical Manual of Mental Disorders (Fourth edition) (DSM-IV) anxiety disorder criteria was required. Efficacy and safety, assessed 2, 2.5, 3, 3.5 and 4 h postdose, included 100 mm Visual Analogue Scale for Anxiety (VAS-Anxiety; primary outcome), 100 mm VAS-Sedation and Time-to-Onset of Action Scale (TOAS), a patient-rated anti-anxiety drug-benefit scale (no [0] to full benefit [10]). Mixed model analysis found significantly greater VAS-A improvement slopes for pregabalin (t = –2.47; P = 0.014) and alprazolam (t = –2.39; P = 0.018). There was a significant improvement versus placebo in the TOAS from 2 h through endpoint in alprazolam patients and from 3 h onward in pregabalin patients. Pregabalin produced significantly greater increases in VAS-Sedation versus placebo from 2.5 h through 4 h (2 h onward for alprazolam). Notably, there was a higher correlation between TOAS and VAS-Sedation (r = +0.58) than VAS-Anxiety (r = –0.50) on Spearman’s analysis. The majority of Adverse Effects (AEs) were mild, and the most frequent for pregabalin, alprazolam, and placebo, respectively, were fatigue (N = 7, 7, 3), dizziness (N = 6, 3, 3), attention disturbance (N = 3, 1, 0), somnolence (N = 3, 0, 0), feeling abnormal (N = 0, 2, 0) and balance disorder (N = 0, 2, 0). These results suggest that onset of clinically meaningful anxiolytic effect after single-dose pregabalin occurs within the first 3—4 h. Additional research is needed to determine whether anxiolytic effect occurs in generalized anxiety disorder populations by day 1 or within 3—4 h post-first dose.

Duloxetine for major depressive episodes in the course of psychotic disorders: an observational clinical trial

Englisch, S., Knopf, U., Scharnholz, B., Kuwilsky, A., Deuschle, M., Zink, M. — Thu, 05 Nov 2009 08:24:39 PST

Patients with psychotic disorders often suffer from intercurrent major depressive episodes (MDE). Case reports suggested successful antidepressive treatment with duloxetine, a selective dual reuptake inhibitor of serotonin and norepinephrine. We initiated this open prospective clinical trial to evaluate efficacy, safety and tolerability of this approach. Patients with a psychotic lifetime diagnosis suffering from mildly severe MDE were treated with duloxetine over a period of 6 weeks. We evaluated effects on mood, monitored the psychotic psychopathology and assessed side effects, basal clinical and pharmacological parameters. Twenty patients were included and experienced a significant improvement of their MDE during the observation period (Calgary Depression Scale for Schizophrenia and Hamilton Depression Scale). Psychotic positive symptoms remained stably absent, while negative syndrome and global psychopathology considerably improved (Positive and Negative Syndrome Scale). In general, the treatment was well tolerated, serum prolactin levels stayed unchanged, but pharmacokinetic interactions with a number of antipsychotic agents were observed. This open prospective evaluation showed antidepressive efficacy of duloxetine in patients with co-morbid psychotic disorders. With regard to the psychotic disorder, the treatment appears to be safe and well tolerable. Further investigations should involve a randomized control group.

Incidence of craving for and abuse of gamma-hydroxybutyric acid (GHB) in different populations of treated alcoholics: an open comparative study

Thu, 05 Nov 2009 08:24:39 PST

Gamma-hydroxybutyric acid (GHB) is a drug currently used for the treatment of alcohol dependence. The aim of our study was to investigate the incidence of craving for and abuse of GHB in 47 patients enrolled and divided into four groups: group A (pure alcoholics), group B (alcoholics with a sustained full remission from cocaine dependence), group C (alcoholics with a sustained full remission from heroin dependence) and group D (alcoholics in a methadone maintenance treatment [MMT] programme). All patients were treated with an oral dose of GHB (50 mg/kg of body weight t.i.d.) for three months. Craving for GHB was statistically significant higher in group B than in group A (P < 0.001), C (P = 0.01) and D (P < 0.001), and in group C than in group D (P < 0.05). Abuse of GHB proved to be statistically significant higher in group B than in group A (P < 0.001) and D (P < 0.01), and in group C than in group A (P = 0.01) and D (P < 0.05). Thus, the administration of GHB in alcoholics with a sustained full remission from heroin or cocaine dependence is not recommended; however, this should not discourage physicians from using GHB for the treatment of pure alcoholics or alcohol dependents following a MMT.

Reduced cooperativeness and reward-dependence in depression with above-normal plasma vasopressin concentration

Thu, 05 Nov 2009 08:24:39 PST

The neuropeptide vasopressin is centrally involved in the regulation of social behaviour and response to stress. We previously found support for a subcategory of depression defined by above-normal plasma vasopressin (AVP) concentration. This subcategory is validated by a positive family history of depression and correlating plasma AVP and cortisol concentrations. The data support the validity of above-normal plasma AVP concentration as a genetically determined biological marker for a subcategory of depression. The aim of the present study was to test whether above-normal plasma AVP concentration in depression is related to personality characteristics reflecting a specific social behaviour style. The data of 78 patients from a previously investigated sample were reanalysed. Fifty-eight patients were available after 2 years, 15 of whom with initially above-normal plasma AVP. The dimensions of the Temperament and Character Inventory (TCI) were scored, with particular focus on the dimensions of Cooperativeness (CO) and Reward-dependence (RD). Normative subjects and other depressed subjects were used as controls. After full remission, patients with initially above-normal AVP had low CO compared with normal and patient controls. During depression, these patients had both low CO and low RD compared with normal controls and low RD compared with patient controls. Low CO is a presumably premorbid trait and reduced RD a state-dependent characteristic in depression with above-normal plasma AVP. The low CO further supports the validity of above-normal plasma AVP concentration as a genetically determined biological marker for a subcategory of depression.

Antimanic potency of typical neuroleptic drugs and affinity for dopamine D2 and serotonin 5-HT2A receptors -- a new analysis of data from the archives and implications for improved antimanic treatments

Harrison-Read, P. — Thu, 05 Nov 2009 08:24:39 PST

Datasets of antimanic potency ratings and receptor-binding affinities [inhibition constants (K_i)] at dopamine D2 and serotonin 5-HT2A brain receptors were accessed from published literature for a large series (n = 24) of typical neuroleptic drugs, many of which are now obsolete and unobtainable. There was a strong positive association between antimanic potency and affinity for D2 receptors, in support of a ‘dopamine-blockade hypothesis’ of antimanic drug action. Taking the series of neuroleptics as a whole, there was no association between antimanic potency and affinity for 5-HT2A receptors. Despite this, within a subsample of typical neuroleptics with low affinity for D2 receptors resembling new generation atypical antipsychotics, a positive association between antimanic potency and affinity for 5-HT2A receptors emerged. This suggests that blockade of brain 5-HT2A receptors plays at least a subsidiary role in the antimanic effects of some typical neuroleptics. Other considerations also suggest that combining drugs to achieve high affinity for and blockade of both dopamine D2 receptors and serotonin 5-HT2A receptors, possibly with additional direct or indirect stimulation of postsynaptic 5-HT1A receptors, might maximize antimanic efficacy.

Risk of cerebrovascular events in elderly users of antipsychotics

Kleijer, B., van Marum, R., Egberts, A., Jansen, P., Knol, W., Heerdink, E. — Thu, 05 Nov 2009 08:24:39 PST

It has been shown that elderly patients with dementia treated with atypical and conventional antipsychotics have a twofold increased risk of cerebrovascular adverse events (CVAEs). To investigate the temporal relationship between exposure to antipsychotics and the risk of CVAE, a case-control analysis nested within a cohort of 26,157 community-dwelling patients (mean age 76 ± 9.7) with at least one antipsychotic prescription was conducted. Data were used from Dutch community pharmacies and hospital discharge records. Five hundred and eighteen cases of hospital admission for CVAE were identified. For each case, four randomly selected controls matched by sex and age were sampled from the cohort. To evaluate the temporal relationship between antipsychotic use and the occurrence of CVAE, two measures were used: the first being a current, recent or past user, and the second for the current users, the duration of use up to the index date. In addition, the cumulative exposure was assessed. Current and recent exposure to antipsychotics were associated with an increased risk of CVAE compared with non-users (odds ratio [OR] 1.7, CI 1.4—2.2). A strong temporal relationship was found; the OR for a history of use less than a week is 9.9 (5.7—17.2). The risk decreases in time and is comparable to non-users after 3 months of use (OR 1.0, CI 0.7—1.3). Cumulative exposure was not associated with an increase in risk. The risk of CVAE in elderly patients associated with antipsychotics is elevated especially during the first weeks of treatment. This risk decreases over time and is back on base level after 3 months of treatment. Chronic use is not associated with CVAE.

Metabolic syndrome in female patients with schizophrenia treated with second generation antipsychotics: a 3-month follow-up

Medved, V., Kuzman, M., Jovanovic, N., Grubisin, J., Kuzman, T. — Thu, 05 Nov 2009 08:24:39 PST

The objective of this study was to determine the occurrence of metabolic abnormalities among previously unmedicated female patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia spectrum disorders and their associations with olanzapine and risperidone treatment. We analysed 94 female patients who were treated with olanzapine or risperidone in the period of 3 months. Analysed variables included fasting glucose, total cholesterol, low-density lipoprotein (LDL), high-density lipoproteins and triglycerides in blood, blood pressure (BP), waist and hip circumferences and body mass index (BMI). At baseline, 14 patients (15%) fulfilled criteria for metabolic syndrome. After 3 months of treatment, 25 patients (27%) fulfilled criteria for metabolic syndrome, and their baseline BMI was the only predictor for its development. Treatment with both antipsychotics was associated with significant increase in waist circumference. Positive family history of diabetes mellitus contributed to a significant greater increase in abdominal obesity, significant higher baseline levels and a borderline significant increase in fasting glucose among olanzapine-treated patients. Olanzapine admission was associated with a significant increase in LDL and risperidone with a significant increase in triglycerides. Metabolic abnormalities seem to be more prevalent in unmedicated female patients with schizophrenia spectrum disorders than expected based on results in general population (adjusted for age and sex). Olanzapine treatment might induce significant alterations in metabolic profiles, especially among patients with positive family history of diabetes, mostly by inducing abdominal obesity. The association of risperidone application and increase in triglyceride level still needs to be determined.

Investigation of serotonin-1A receptor function in the human psychopharmacology of MDMA

Hasler, F., Studerus, E., Lindner, K., Ludewig, S., Vollenweider, F. — Thu, 05 Nov 2009 08:24:39 PST

Serotonin (5-HT) release is the primary pharmacological mechanism of 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) action in the primate brain. Dopamine release and direct stimulation of dopamine D2 and serotonin 5-HT_2A receptors also contributes to the overall action of MDMA. The role of 5-HT_1A receptors in the human psychopharmacology of MDMA, however, has not yet been elucidated. In order to reveal the consequences of manipulation at the 5-HT_1A receptor system on cognitive and subjective effects of MDMA, a receptor blocking study using the mixed beta-adrenoreceptor blocker/5-HT_1A antagonist pindolol was performed. Using a double-blind, placebo-controlled within-subject design, 15 healthy male subjects were examined under placebo (PL), 20 mg pindolol (PIN), MDMA (1.6 mg/kg b.wt.), MDMA following pre-treatment with pindolol (PIN-MDMA). Tasks from the Cambridge Neuropsychological Test Automated Battery were used for the assessment of cognitive performance. Psychometric questionnaires were applied to measure effects of treatment on core dimensions of Altered States of Consciousness, mood and state anxiety. Compared with PL, MDMA significantly impaired sustained attention and visual-spatial memory, but did not affect executive functions. Pre-treatment with PIN did not significantly alter MDMA-induced impairment of cognitive performance and only exerted a minor modulating effect on two psychometric scales affected by MDMA treatment (‘positive derealization’ and ‘dreaminess’). Our findings suggest that MDMA differentially affects higher cognitive functions, but does not support the hypothesis from animal studies, that some of the MDMA effects are causally mediated through action at the 5-HT_1A receptor system.

Lack of association between AKT1 variances versus clinical manifestations and social function in patients with schizophrenia

Liu, Y., Huang, C., Wu, P., Chang, Y., Huang, C., Lane, H. — Thu, 05 Nov 2009 08:24:39 PST

The elucidation of genotype-phenotype relationships in psychiatric research is at an early stage. V-akt murine thymoma viral oncogene homolog 1 (AKT1) is a serine/threonine kinase known as protein kinase B. Emerging studies have implicated the role of AKT1 in pathogenesis of schizophrenia; however, the findings have not been consistent. This study aims to examine the association of AKT1 polymorphisms with drug-free and post-treatment symptomatology and social function in patients with schizophrenia. One hundred and twenty newly hospitalised patients with acutely exacerbated schizophrenia who had never been treated by atypical antipsychotics were recruited. They received optimal treatment of risperidone for up to 42 days in the inpatient research unit. Clinical manifestations were monitored by Positive and Negative Syndrome Scale (PANSS) and social function by Nurses’ Observation Scale for Inpatients Evaluation (NOSIE). Patients were genotyped for eight AKT1 Single Nucleotide Polymorphism (SNPs), which have been previously investigated for association with schizophrenia. At drug-free status and after best possible treatment of risperidone, genotypes of each SNP did not influence performances in NOSIE, PANSS-total, -positive, -negative and -general psychopathology profiles. These results suggest that AKT1 does not play a significant role in clinical and functional manifestations in patients with schizophrenia who receive risperidone treatment. Future research should also focus on the relationships between genotypes of other susceptibility genes and phenotypes or functional outcomes of schizophrenia.

Sex-related differential response to clomipramine treatment in a rat model of depression

Thu, 05 Nov 2009 08:24:39 PST

Research in affective disorders is often performed without considering sex differences, although women are predominantly affected. Consequently, the potential sex-dependent action of antidepressants remains elusive. We investigated whether Flinders sensitive line (FSL) of rats, a model of depression, would present sex-differentiated responses to antidepressant treatment. FSL and Sprague—Dawley rats were treated with clomipramine 10 mg/kg/day for 14 days. Subsequently, they were subjected to either a single session of the forced swim test or an estimation of serotonergic function in the prefrontal cortex, hippocampus, amygdala and hypothalamus. Male FSL displayed increased immobility duration, decreased active behaviours, increased serotonin tissue levels and a reduced serotonin turnover rate in most brain areas studied. Female FSL showed a distinct profile, consisting of decreased immobility latency, increased climbing duration, limited serotonergic deviations and no difference in the serotonin turnover rate in comparison with controls. Interestingly, despite baseline differences, clomipramine treatment reversed all relevant behavioural responses and increased the serotonin turnover rate in both sexes. However, the latter effect was remarkably more pronounced in females. It is concluded that, in this animal model of depression, chronic clomipramine treatment attenuated baseline sex differences in the phenotype while maintaining or intensifying the sex differentiation in the serotonergic endophenotype.

Outcomes for schizophrenia patients with clozapine treatment: how good does it get?

Wheeler, A., Humberstone, V., Robinson, G. — Thu, 05 Nov 2009 08:24:39 PST

The objective of this study was to describe the extent/change (2000—2004) of clozapine prescribing in schizophrenia in New Zealand and examine the outcomes associated with increasing treatment duration, and vs. those who discontinue clozapine. Consecutive chart reviews were conducted for adult outpatients in Auckland/Northland regions (T1 = 31 March 2000, T2 = 31 October 2001, T3 = 31 March 2003, T4 = 31 October 2004). Data collected included: patient characteristics, social/functional indicators, diagnosis, duration of illness, psychiatric admissions and treatment information (psychotropic medication, dose, route of administration). Between 2000 and 2004, clozapine for schizophrenia increased from 21.0% to 32.8%. Of those prescribed clozapine at T1, 86.1% were engaged with community services at T4 and 93.2% still prescribed clozapine. Continuing clozapine treatment (vs. other treatment) led to a trend to higher rates of regular occupational activity (37% vs. 14.3%) and lower rates of compulsory treatment (25.1% vs. 46.4%) and significantly lower hospitalisation rates (mean = 0.6 vs. mean = 3.1). For those prescribed clozapine at T4, increasing treatment duration (≤10 months, 2—3 years, >3 years) led to a trend to higher rates of living independently (18% vs. 29.2% vs. 34%) and regular occupational activity (26.2% vs. 32.6% vs. 37.5%), and significantly reduced compulsory treatment (44.3% vs. 36.9% vs. 28.6%) and hospitalisation rates in the previous 18 months (1.5 vs. 0.5 vs. 0.2). Clozapine use increased significantly over 4.5 years to expected rates of treatment-resistant schizophrenia. Low clozapine discontinuation rates were found and continuing treatment was associated with real-world improvements in functional and clinical outcomes. These findings support the recommendation of prolonged clozapine trials to improve cost-effectiveness in the most seriously unwell schizophrenia patients.

Review: Problems associated with long-term treatment with selective serotonin reuptake inhibitors

Moret, C., Isaac, M., Briley, M. — Thu, 05 Nov 2009 08:24:39 PST

Although the selective serotonin reuptake inhibitors (SSRIs), which are now widely used as a first-line treatment for depression and many other psychiatric conditions, are generally well tolerated, they are not devoid of side effects. Most short-term treatment-related side effects of SSRIs are transient and disappear after a few days or weeks. However, following long-term treatment with the SSRIs, some serious adverse events may occur. Some of them can be difficult to recognise because they can resemble residual symptoms of depression. The most serious can be life threatening. They all have a negative influence on the patient’s quality of life and are frequently a prime reason for a lack of long-term compliance with the associated increased risk of recurrence of a depressive episode. This article is an overview of the more common adverse events, which are seen with non-acute treatment with the SSRIs.

The effects of opioid receptor blockade on experimental panic provocation with CO 2

Esquivel, G., Fernandez-Torre, O., Schruers, K., Wijnhoven, L., Griez, E. — Thu, 05 Nov 2009 08:24:39 PST

Several reports have linked, among other aspects, the role of an opioid system in respiratory physiology with underlying mechanisms of panic attacks. The involvement of the opioid system in experimental panic is to be further probed. This study aimed to determine whether opioid blockade would increase panic-related symptomatology on provocation with 35% CO₂ inhaled by healthy volunteers. Participants in a double-blind, randomised crossover design orally received either 50 mg of naltrexone or placebo. Most subjects undertook a double inhalation of 35% CO₂ one hour after pre-medication, and a separate group did so after five hours. The reactivity to CO₂ and the symptoms elicited by naltrexone alone were measured. Among other findings, naltrexone pre-medication alone elicited significant increments in panic-related symptoms. Responses to CO₂ were not significantly different between conditions in either group. These preliminary findings suggest that exposure to opioid blockade alone can potentially elicit symptoms that resemble panic, however, without modifying the response to experimental panic provocation with 35% CO₂.

Cannabidiol for the treatment of psychosis in Parkinson's disease

Thu, 05 Nov 2009 08:24:39 PST

The management of psychosis in Parkinson’s disease (PD) has been considered a great challenge for clinicians and there is a need for new pharmacological intervention. Previously an antipsychotic and neuroprotective effect of Cannabidiol (CBD) has been suggested. Therefore, the aim of the present study was to directly evaluate for the first time, the efficacy, tolerability and safety of CBD on PD patients with psychotic symptoms. This was an open-label pilot study. Six consecutive outpatients (four men and two women) with the diagnosis of PD and who had psychosis for at least 3 months were selected for the study. All patients received CBD in flexible dose (started with an oral dose of 150 mg/day) for 4 weeks, in addition to their usual therapy. The psychotic symptoms evaluated by the Brief Psychiatric Rating Scale and the Parkinson Psychosis Questionnaire showed a significant decrease under CBD treatment. CBD did not worsen the motor function and decreased the total scores of the Unified Parkinson’s Disease Rating Scale. No adverse effect was observed during the treatment. These preliminary data suggest that CBD may be effective, safe and well tolerated for the treatment of the psychosis in PD.

Improved stress response in bipolar affective disorder with adjunctive spironolactone (mineralocorticoid receptor antagonist): case series

Juruena, M., Gama, C., Berk, M., Belmonte-de-Abreu, P. — Thu, 05 Nov 2009 08:24:39 PST

The psychopathologies underlying affective disorders are thought to involve persistent changes in the expression and function of both mineralocorticoid receptors and glucocorticoid receptors in the hippocampus. In addition, exposure to stressful stimuli can precipitate episodes in vulnerable individuals. The aim of this study is to determine if spironolactone as an adjunctive therapy is effective in improving residual symptoms in bipolar disorder. Four cases of euthymic bipolar disorder (BD) patients were treated with spironolactone as an adjunctive therapy in a private treatment sector. All patients met the DSM-IV diagnosis criteria for bipolar disorder. Clinical response was assessed retrospectively using the Clinical Global Impression Scale for Improvement. Spironolactone was effective in all patients. The four cases illustrate a clinical response to residual symptoms and improvement in stress response after use of spironolactone as an adjunctive therapy in BD. This pilot case series suggests reducing in residual symptoms, with spironolactone as an adjunctive therapy in these DSM-IV BD patients. Mineralocorticoid receptors antagonists’ role in reducing stress-induced symptoms deserves further investigation through placebo-controlled trials.

A 60-year-old woman with agitation and psychosis following ingestion of dextromethorphan and opioid analgesics

Jamison, S., Vasudeva, S. — Thu, 05 Nov 2009 08:24:40 PST

A patient presented with agitation, paranoia, and psychosis following ingestion of dextromethorphan, propoxyphene, and hydrocodone, a previously unreported combination. Symptoms resolved with antipsychotics and cessation of offending drugs. The pharmacodynamics of dextromethorphan and the opioids, including drug interactions are discussed, and several potential mechanisms for the production of the patient’s symptoms are proposed.

The potential relationship between QTc interval prolongation and ziprasidone treatment: three cases

Eker, S., Sarandol, A., Akkaya, C., Sivrioglu, E., Kirli, S. — Thu, 05 Nov 2009 08:24:40 PST

QTc interval prolongation may appear as a consequence of both typical and atypical antipsychotic treatments. Ziprasidone, which is effective in treating schizophrenia, is associated with QTc prolongation. Although the prolongation of QTc with ziprasidone treatment is often pronounced, there is a scarce number of cases reported about the relationship between ziprasidone and QTc prolongation. Of the three cases presented in this case series, two cases showed values exceeding 0.50 s with ziprasidone treatment.

Positive interference of the analgesic nefopam in the urine immunoassay for benzodiazepines in a secure setting

Reid, K. — Thu, 05 Nov 2009 08:24:40 PST

An inpatient on a secure unit with a history of bipolar affective disorder and physical complaints including pain was prescribed carbamazepine, quetiapine, dihydrocodeine, nefopam, paracetamol and various aperients. A benzodiazepine urine test by immunoassay was positive. Initial literature searches did not suggest a candidate drug for positive interference. Other explanations were excluded. Positive results continued, despite room searches and other disruptive security measures. Further literature searches revealed one experimental series demonstrating positive interference of nefopam in the relevant assay. Benzodiazepine assays were negative after cessation of nefopam. This is the first such clinical case to our knowledge.

Olanzapine treatment in Jarisch-Herxheimer reaction due to neurosyphilis with dementia: a case report

Ates, M., Algul, A., Gecici, O., Semiz, U., Yilmaz, O., Gulsun, M. — Thu, 05 Nov 2009 08:24:40 PST

We discussed a neurosyphilis case who had a risky sexual intercourse history nearly 10 years ago. After the neurosyphilis diagnosis, the patient has clinical symptoms of a demential case starting as a typical manic episode and Jarisch-Herxheimer reaction because of intravenous penicillin treatment that has improved with olanzapine treatment.

Lamotrigine-induced obsessional symptoms in a patient with bipolar II disorder: a case report

Kuloglu, M., Caykoylu, A., Ekinci, O., Yilmaz, E. — Thu, 05 Nov 2009 08:24:40 PST

Lamotrigine is an anticonvulsant that appears to have a mainly antidepressant effect and is indicated for the maintenance treatment of bipolar depression. Literature associated with obsessional symptoms related to lamotrigine treatment is limited. We report the emergence of obsessive symptoms during treatment with lamotrigine in a patient who subsequently experienced significant improvement after dose reduction and stopping of this medication. The obsessive symptoms associated with lamotrigine treatment were observed after the lamotrigine dose was increased to 100 mg/day. The possible mechanisms, including inhibition on the presynaptic release of glutamate and alteration of striatal dopamine uptake, are discussed. It is unclear why lamotrigine induces obsessions in some patients. Controlled studies are necessary to identify the population at risk for obsessionality in bipolar illness following treatment with lamotrigine and to investigate a possible dose—response relationship between obsessive symptoms and lamotrigine.

Book Review: Clinical Guide to the Diagnosis and Treatment of Mental Disorders Michael First, Allam Tasman, Wiley, Price: {pound}50

Mitchell, A. — Thu, 05 Nov 2009 08:24:40 PST

Erratum

Thu, 05 Nov 2009 08:24:40 PST

A Tint, P M Haddad, and I M Anderson. The effect of rate of antidepressant tapering on the incidence of discontinuation symptoms: a randomised study. Journal of Psychopharmacology first published this on May 30, 2008 as DOI: 10.1177/0269881107087488. This version is no longer available. The version of record is published in Vol. 22 No 3, DOI 10.1177/0269881107081550