Levetiracetam for the treatment of alcohol withdrawal syndrome: a multicenter, prospective, randomized, placebo-controlled trial.

BACKGROUND: Treatment of alcohol withdrawal syndrome (AWS) with benzodiazepines is limited by risk of abuse, intoxication, respiratory problems, and liver toxicity. Alternatives such as carbamazepine and valproate may also have safety problems, such as hepatotoxicity or central nervous adverse effects. We therefore investigated the safety and efficacy of levetiracetam (LV), a newer antiepileptic with a potentially favorable adverse-effect profile, for the treatment of AWS. METHODS: One hundred six patients were enrolled in a prospective, randomized, double-blind, multicenter, placebo-controlled trial. Levetiracetam was administered in a fixed dose schedule over 6 days. Diazepam was added when symptom triggered as rescue medication. Severity of the AWS was measured with the AWS and Clinical Institute Withdrawal Assessment Scale. RESULTS: Although tolerability and safety data were similar in the LV group when compared with placebo, the total daily and weekly dose of diazepam as rescue medication and the severity of alcohol withdrawal symptoms did not differ significantly between groups. CONCLUSION: Our data so far do not support an additional effect of LV on the reduction of alcohol withdrawal symptoms.

Depressive mood changes and psychiatric symptoms during 12-month low-dose interferon-alpha treatment in patients with malignant melanoma: results from the multicenter DeCOG trial.

The purpose of the present study was to evaluate the incidence, spectrum and extent of psychiatric symptoms in patients with malignant melanoma (MM) before and during adjuvant treatment with interferon-alpha (IFN-alpha). 850 patients with cutaneous MM of > or =1.5 mm tumor thickness received standard low-dose IFN-alpha 2a in this prospective multicenter trial of the Dermatologic Cooperative Oncology Group (DeCOG). Psychiatric symptoms were evaluated at baseline and after 3, 6, and 12 months with the Beck Depression Inventory (BDI) and the Symptom Check List 90-Revised (SCL 90-R). In all, 282 patients completed all questionnaires. Mean BDI depression scores increased significantly during the first 6 months of IFN-alpha treatment (P < or =0.001), followed by a mild but not significant decrease. Also mean SCL 90-R scores increased significantly during the first 3 months of adjuvant treatment with IFN-alpha (P< or =0.001) and remained elevated until month 12 (P< or =0.001). Only 5% developed BDI scores >10, indicating a clinically significant depressive syndrome and only 1.4% reached a BDI score > or =18, indicating a moderate to severe depressive syndrome. Patients, who dropped-out early from psychiatric reasons, had significantly increased BDI and SCL-90R scores at baseline. Women scored higher in both scales before and during treatment if compared with men. In conclusion, adjuvant treatment with IFN-alpha was associated with a significant increase of BDI- and SCL 90-R scores. A higher pretreatment depression score was found to be a risk factor for an early drop-out during therapy. Pretreatment screening and an interdisciplinary care of the patients is recommended.

Hepatitis C treatment in "difficult-to-treat" psychiatric patients with pegylated interferon-alpha and ribavirin: response and psychiatric side effects.

UNLABELLED: We investigated and compared the results of treating the chronic hepatitis C (HCV) infection of different groups of psychiatric-risk patients and controls with pegylated interferon alpha (pegIFN-alpha) plus ribavirin. Seventy patients were prospectively screened for psychiatric disorders. Seventeen patients without psychiatric diseases or drug addiction (controls), 22 patients with psychiatric disorders, 18 patients who had received methadone substitution treatment and 13 patients who were former drug users were treated with pegIFN-alpha plus ribavirin. Sustained virological response (SVR), adherence, and psychiatric side effects (using the Montgomery-Asberg Depression Rating Scale and the Brief Psychiatric Rating Scale) in the groups were compared. An SVR was found in 58.6% of all patients: 58.8% of the controls, 50% of psychiatric patients, 72.2% of methadone patients, and 53.8% of former drug users. Methadone-substituted patients and former drug users had significantly higher dropout rates. Scores for neither depressive nor psychotic symptoms differed significantly between groups during treatment. However, the controls had lower pretreatment scores, followed by a significant higher increase to maximum scores. A stepwise logistic regression model showed that only genotype, not group (control, psychiatric, methadone, or former drug abuse), type of psychiatric diagnosis (affective disorder, personality disorder, or schizophrenic disorder), depression scores before and during treatment, change in depression score, antidepressive treatment, sex, or liver enzymes before treatment, was associated with SVR. CONCLUSION: In an interdisciplinary treatment setting psychiatric diseases and/or drug addiction did not negatively influence psychiatric tolerability of and antiviral response rate to HCV treatment with pegIFN-alpha and ribavirin.

Current schizophrenia drugs: efficacy and side effects.

Over the course of the past decade, the acceptance of several second-generation antipsychotics (SGAs) as effective medication for the treatment of schizophrenia has led to some changes. SGAs have a lower risk of inducing extrapyramidal side effects and tardive dyskinesia compared with first-generation antipsychotics, and have been said to be more successful in long-term treatment and tolerability. They also significantly improve the quality of life of schizophrenic patients. However, during treatment with SGAs other adverse effects can occur, such as weight gain, metabolic changes, sexual dysfunction and QTc-prolongation, significantly affecting the patient's physical health. Consequently, these side effects might be the reason that a high proportion of patients discontinue treatment with SGAs. Thus, from the authors' view, optimising individualised treatment implies increasing the efficacy of current schizophrenia drugs. This can be achieved by finding clinical or pharmacogenetic predictors for the most appropriate drug or drug combination, and by improving side-effect management in combination with non-pharmacological interventions in order to increase patients' quality of life and treatment compliance, possibly resulting in a better long-term outcome.

Neuroprotective agents in schizophrenia and affective disorders.

With the exception of dementia, the use of neuroprotective agents in psychiatric disorders is not yet well established. However, recent data from brain imaging studies and clinical trials support the view that neurodegenerative mechanisms may play a role in the pathophysiology of schizophrenia and affective disorders. Further evidence for the use of neuroprotective agents can be drawn from the findings that second-generation antipsychotics, mood stabilizers and antidepressants have been shown to have neuroprotective effects in vitro and in vivo. Neuroprotective agents as add-on therapies (e.g., modafinil, erythropoietin, glycine, D-serine, memantine and celecoxib) are currently being evaluated in schizophrenia and related disorders. This paper reviews the current options for neuroprotective treatment approaches focusing on schizophrenia and affective disorders.

Prevention of interferon-alpha associated depression in psychiatric risk patients with chronic hepatitis C.

BACKGROUND/AIMS: Interferon-alpha (IFN-alpha) induced depression is a major limitation for the treatment of chronic hepatitis C, especially for patients with psychiatric disorders. We prospectively studied the efficacy of a pre-emptive treatment with the antidepressant citalopram to prevent depression during hepatitis C treatment with pegylated IFN-alpha-2b plus ribavirin. METHODS: 14 HCV infected patients with psychiatric disorders received a prophylactic medication with citalopram (20mg/day) before and during therapy with IFN-alpha. The incidence of major depression was compared with 22 HCV infected patients with psychiatric disorders (group B; n=11) and without psychiatric risk factors (group C; n=11), who underwent IFN-alpha treatment without a pre-emptive antidepressant therapy. Depression was diagnosed by DSM-IV criteria. RESULTS: Pre-treatment of psychiatric patients with citalopram significantly reduced the incidence of major depression during the first 6 months of antiviral treatment as compared to the two control groups (group A 14% vs. 64% and 55% in group B and C; log-rank 6.89; df=2; P=0.032). Patients who developed symptoms of major depression during IFN therapy could also be improved by antidepressive treatment. CONCLUSIONS: Our open label pilot study, though small, clearly indicates that IFN alpha induced depression in psychiatric risk patients can be ameliorated by both the use of antidepressants as well as by intensive psychiatric care. However, larger, double blind placebo controlled trials in other patient populations are required to confirm these preliminary findings.