Adjunctive lithium treatment in the prevention of suicidal behavior in patients with depression and comorbid personality disorders.

OBJECTIVE: Patients with both major depression and personality disorders have a high risk of suicidal behavior. Lithium is meant to have anti-suicidal properties in patients with affective disorders. The anti-suicidal effect of lithium in patients with affective disorders and comorbid personality disorders has not been investigated yet. METHODS: A post-hoc analysis of a subsample of patients with depression and comorbid personality disorder (PD) and a recent suicide attempt (n = 19) from the prospective, placebo-controlled lithium intervention study (N = 167), was conducted. RESULTS: Three patients in the lithium group (n = 8) and two patients in the placebo group (n = 11) presented a suicide attempt throughout the course of the study. No differences related to suicidal behavior could be detected between the placebo group and the group with lithium intervention. CONCLUSIONS: On the basis of the small sample size, among patients with comorbid PD, lithium does not seem to have an effect on suicidal behavior in contrast to patients with affective disorders without comorbid PD.

Long-term outcome after lithium augmentation in unipolar depression: focus on HPA system activity.

BACKGROUND: Lithium augmentation is a first-line strategy for depressed patients resistant to antidepressive therapy, but little is known about patients' subsequent long-term course or outcome predictors. We investigated long-term outcomes of unipolar depressed patients who had participated in a study on the effects of lithium augmentation on the hypothalamic-pituitary-adrenocortical system using the combined dexamethasone/corticotrophin-releasing hormone (DEX/CRH) test. METHODS: Twelve to 28 months (mean 18.6 +/- 4.6 months) after lithium augmentation, 23 patients were assessed with a standardized interview, of which 18 patients had complete DEX/CRH test results. Relapse was diagnosed by DSM-IV criteria (Structured Clinical Interview for DSM-IV; SCID I). RESULTS: Only 11 patients (48%) had a favorable follow-up, defined as absence of major depressive episodes during the observation period. Patients with a favorable and an unfavorable course did not differ in clinical or sociodemographic parameters, endocrinological results or continuation of lithium. However, fewer previous depressive episodes tended to correlate (p = 0.09) with a favorable course. CONCLUSION: Results from studies using the DEX/CRH test to predict relapse in depressed patients treated with antidepressants were not replicated for lithium augmentation. Our finding could reflect the elevation of DEX/CRH results by lithium, independent of clinical course. Limitations of the study are its small sample size, the heterogeneous clinical baseline conditions and the lack of lithium serum levels. The fact that lithium continuation did not predict the course might be related to the difference between the efficacy of lithium in controlled studies and its effectiveness in naturalistic settings.

Atypical antipsychotics and pituitary neoplasms in the WHO database.

Amisulpride and risperidone are potent dopamine D2 receptor blocking atypical antipsychotics that can cause hyperprolactinemia. Preclinical evidence shows that chronic administration of antipsychotics can cause pituitary adenomas in female mice. To investigate the clinical relevance in this finding, reports of pituitary neoplasms in the WHO adverse drug reaction (ADR) database were reviewed. Amisulpride and risperidone [corrected] had among the highest Information Component (IC) scores for benign pituitary neoplasm; amisulpride (IC = 3.31, IC025 = 1.83, 5 reports) and risperidone (IC = 4.03, IC025 = 3.33, 19 reports), and not otherwise specified (NOS) pituitary neoplasm: amisulpride (IC = 2.69, IC025 = 0.70, 3 reports) and risperidone (IC = 4.49, IC025 = 3.86, 23 reports). We conclude that there is a need for prospective studies to confirm causality and suggest that clinicians, until then, would consider a pituitary adenoma in patients experiencing severe hyperprolactinemia or associated symptoms when receiving potent D2 antagonists [corrected]

Impact of myeloperoxidase and NADPH-oxidase polymorphisms in drug-induced agranulocytosis.

Therapy of the atypical antipsychotic drug clozapine is limited by a comparatively high incidence of agranulocytosis in 0.8% of patients. This severe side effect is possibly based on the clozapine-mediated stimulation of cytokines and soluble cytokine receptors release, followed by induction of granulocyte proliferation and induction of myeloperoxidase (MPO) and NADPH-oxidase. Because NADPH-oxidase/MPO may oxidize clozapine to highly reactive nitrenium ions, we investigated the role of hereditary polymorphisms in the NADPH oxidase/myeloperoxidase system in agranulocytosis patients who received clozapine (n = 49), ticlopidine (n = 11), and other drugs prior to the event. The low active MPO -436A allelic variant frequency was 22.2% in cases and 19.9% in controls, but AA carriers were overrepresented among cases compared with the sum of AG and GG-carriers (odds ratio 4.16, 95% confidence limits 0.86-20.3, P = 0.056). Particularly in clozapine-induced agranulocytosis, this finding was most pronounced (P = 0.04). In the CYBA gene, encoding the p22phox subunit of the NADPH-oxidase, 2 polymorphisms were investigated. C242T (His72Tyr) had an allele frequency of 31.9% and 32.2% (P = NS) and A640G in the 3'-UTR was less frequent in cases (48.7%) than controls (60.0%), odds ratio 0.63 (0.39-1.02), P = 0.048. CYBA 640GG-carriers were marginally less frequent in cases compared with controls (28.2% vs. 38.7%, P = 0.062). Sequencing the entire coding region of the NADPH subunit CYBB (gpS1phase) disclosed that CYBB is a highly conserved gene, which does not represent a risk factor for clozapine-induced agranulocytosis. The impact of the polymorphic myeloperoxidase, however, needs further verification to predict a patient's risk to develop drug-induced agranulocytosis.