International clinical psychopharmacology
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Int Clin Psychopharmacol · Jul 2010
Meta AnalysisEscitalopram versus serotonin noradrenaline reuptake inhibitors as second step treatment for patients with major depressive disorder: a pooled analysis.
The objective of this study was to evaluate the efficacy and tolerability of escitalopram versus serotonin and noradrenaline reuptake inhibitors (SNRIs) as second step treatment (defined operationally as poor response or intolerability to an antidepressant) for major depressive disorder (MDD). Results from all eligible head-to-head clinical trials of MDD (which excluded patients who earlier failed two or more antidepressants) sponsored by Lundbeck or Forest comparing escitalopram and SNRIs (venlafaxine and duloxetine) were pooled. A second step treatment subgroup was identified, defined as patients treated earlier with any antidepressant in the 6-month period before baseline. ⋯ Escitalopram showed a better tolerability profile with lower all-cause withdrawals from study (9 vs. 23%, P<0.04) and lower withdrawals because of adverse events (2 vs. 17%, P<0.003). In conclusion, escitalopram is associated with a better efficacy and tolerability profile than SNRIs (duloxetine and venlafaxine) when used as a second step treatment in patients with MDD. These results should be confirmed in prospective randomized clinical trials.
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Int Clin Psychopharmacol · Jul 2010
Multicenter StudyThe impact of catechol-O-methyltransferase SNPs and haplotypes on treatment response phenotypes in major depressive disorder: a case-control association study.
Catechol-O-methyltransferase (COMT) has been suggested to be involved in the pathogenesis and pharmacological treatment of affective disorders. The nonsynonymous single nucleotide polymorphism (SNP) in exon 4 (Val108/158Met; rs4680) influences the COMT enzyme activity. Inconsistent results were found between Val158Met polymorphism (rs4680) and treatment response phenotypes in genetic association studies. ⋯ The C-C-A haplotype of these SNPs was overrepresented (almost four-and eight-fold) in the responders compared with the nonresponders and controls, respectively, after Bonferroni correction (corrected sim P=0.048, 0.0001, respectively). Both nonsynonymous and synonymous SNPs within haplotypes may be more relevant than the single SNP in conferring MDD susceptibility and treatment response phenotypes. Despite the limited power of our analysis, this finding suggests that the polymorphic COMT gene that influences catecholaminergic neurotransmission may play a role in the individual response to antidepressants.
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Int Clin Psychopharmacol · Sep 2009
Multicenter Study Comparative Study Clinical TrialEfficacy and tolerability of switching to ziprasidone from olanzapine, risperidone or haloperidol: an international, multicenter study.
To compare the effectiveness of a switch from haloperidol (N=99), olanzapine (N=82), or risperidone (N=104) to 12 weeks of treatment with 80-160 mg/day ziprasidone in patients with stable schizophrenia or schizoaffective disorder. Stable outpatients with persistent symptoms or troublesome side effects were switched using one of three 1-week taper/switch strategies as determined by the investigator. Efficacy was assessed using the Brief Psychiatric Rating Scale score, Clinical Global Impression, Positive and Negative Symptom Scale, Montgomery-Asberg Depression Rating Scale, and the Global Assessment of Functioning Scale, and tolerability by using standard measures of weight change, extrapyramidal symptoms, and laboratory findings. ⋯ At week 12, a switch to ziprasidone resulted in statistically significant improvement from baseline on the Brief Psychiatric Rating Scale score, Clinical Global Impression-Improvement, Positive and Negative Symptom Scale, and Global Assessment of Functioning scales, reduction in extrapyramidal symptoms and a neutral impact on metabolic parameters. Switch from olanzapine and risperidone resulted in weight reduction and from haloperidol in some weight increase. In conclusion, oral ziprasidone of 80-160 mg/day with food was a clinically valuable treatment option for stable patients with schizophrenia or schizoaffective disorder experiencing suboptimal efficacy or poor tolerability with haloperidol, olanzapine, or risperidone.
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Int Clin Psychopharmacol · Jul 2009
Multicenter Study Controlled Clinical TrialThe efficacy of pregabalin and benzodiazepines in generalized anxiety disorder presenting with high levels of insomnia.
The objective of this study was to assess the impact of high levels of insomnia on response to pregabalin (PGB) in patients with generalized anxiety disorder (GAD). Pooled data were analyzed from six double-blind, placebo-controlled, 4- to 6-week trials of outpatients who met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) criteria for GAD with a minimum Hamilton Rating Scale for Anxiety (HAM-A) score = 18. Response was evaluated for three fixed-dose PGB groups (150, 300-450, 600 mg/day), and for a benzodiazepine group (alprazolam or lorazepam). ⋯ In the high-insomnia subgroup, treatment with PGB significantly (P<0.001) improved the HAM-D insomnia factor scores on both the 300-450 mg (-2.73) and 600 mg (-2.35) doses, and on benzodiazepines (-2.52) compared with placebo (-1.51); improvement on PGB 150 mg (-1.69) was not significant. Rates of treatment-emergent insomnia were lower on PGB compared with placebo in both the high- and low-insomnia subgroups. In conclusion, PGB was well tolerated, and improved overall anxiety symptoms, while specifically improving insomnia in patients with GAD presenting with high levels of concurrent insomnia.
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Int Clin Psychopharmacol · May 2009
Impact of gastrointestinal symptoms on response to pregabalin in generalized anxiety disorder: results of a six-study combined analysis.
The objective of the study was to evaluate the response of generalized anxiety disorder (GAD) patients with prominent gastrointestinal (GI) symptoms to pregabalin (PGB) treatment. Data were pooled from six double-blind, placebo (PBO)-controlled, 4-6 week trials in outpatients who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria for GAD with a minimum Hamilton Anxiety Rating Scale (HAM-A) total score of 20. Treatment response was evaluated for three PGB fixed-dosage groups: 150, 300-450, and 600 mg/day, and for fixed doses of a benzodiazepine (alprazolam, 1.5 mg/day; lorazepam, 6 mg/day). ⋯ In the GI-high subgroup, treatment with a benzodiazepine was not associated with significant endpoint reduction in either the HAM-A total score or the HAM-A item-11 score. Patients in the GI-high subgroup had higher discontinuation rates when treated with benzodiazepines, whereas treatment with PGB 300-600 mg/day was not associated with treatment-emergent worsening in GI symptoms compared with placebo. Treatment with PGB improved overall levels of anxiety, as well as specifically improving GI symptoms.