Mirtazapine monotherapy versus combination therapy with mirtazapine and aripiprazole in depressed patients without psychotic features: a 4-week open-label parallel-group study.

BACKGROUND: There is preliminary evidence that the atypical antipsychotic aripiprazole, which is a partial agonist at D(2) and 5-HT(1A) receptors and a potent antagonist at 5-HT(2A) receptors, may be useful as an augmentation strategy in treatment-resistant depression. METHOD: In this 4-week open-label non-randomized parallel-group study, the safety and efficacy of aripiprazole as add-on treatment strategy in patients suffering from non-delusional depression was investigated. Forty drug-free depressed inpatients without psychotic symptoms (13 men, 27 women), suffering from a major depressive episode or bipolar disorder, depressive state (DSM-IV criteria), were included in the study. The patients were treated either with mirtazapine monotherapy (45 mg/day) or combination therapy (mirtazapine 45 mg/day plus aripiprazole 15 mg/day) for 4 weeks. Safety and efficacy were assessed weekly using the Hamilton Depression Rating Scale, the Simpson-Angus Scale and the Barnes Akathisia Scale. RESULTS: Mirtazapine monotherapy and combined treatment with mirtazapine and aripiprazole showed comparable antidepressant effects as assessed at the endpoint of the study period. However, additional administration of aripiprazole accelerated the onset of antidepressant action in patients suffering from treatment-resistant depression. Additive use of aripiprazole reduced the mirtazapine-induced increase in the body mass index. Moreover, mirtazapine had favourable effects on aripiprazole-induced akathisia. No other extrapyramidal side effects were seen in the combination therapy group. CONCLUSION: Combined therapy with mirtazapine and aripiprazole is a safe and well-tolerated treatment option which may be useful especially in treatment-resistant depression. Double-blind controlled studies are needed to further explore the efficacy and safety of aripiprazole in depressed patients.

Neurological soft signs and neuropsychological performance in patients with first episode schizophrenia.

Neurological soft signs and neuropsychological (NP) impairments are prevalent in schizophrenic patients. However, the relationship of these deficits is rarely studied, and it remains controversial in what way soft signs influence NP performance. The Neurological Evaluation Scale (NES) and a comprehensive neuropsychological test battery were used to assess soft signs and cognitive functions in 61 first-episode schizophrenic patients. The NP test battery included tests such as the California Verbal Learning Test, the Continuous Performance Test, the Span of Apprehension Test, the Stroop Color-Word Test, the Trail-Making Test and the Wisconsin Card Sorting Test. The NP tests were also administered to 87 healthy controls. The first-episode schizophrenic patients were split along the median of their NES total score (SS- vs. SS+). The level of NP performance and the differences in relative performance (shape of the NP profile) on NP functions between the two groups were assessed. The two groups (SS- vs. SS+) did not differ in any demographic or clinical variable. However, they differed in the level of their NP performance (profile mean) but did not show differential deficits in NP performance (profile shape). Neurologic soft signs influence NP performance and are correlated to a generalized NP deficit rather than to any specific NP functions.

Neurocognitive functioning in patients with first-episode schizophrenia : results of a prospective 5-year follow-up study.

To assess the course of neuropsychological (NP) impairment in schizophrenia, 71 patients with first episode (FE) schizophrenia and 71 healthy controls were given a comprehensive battery of NP tests at index assessment, after a 2-year and after a 5-year follow-up period. By means of the z-score standardization, summary scores for verbal intelligence (VBI), spatial organisation (SPT), verbal fluency (VBF), Verbal learning (VBL), semantic memory (SEM), visual memory (VIM), delay/retention rate (DEL), short-term memory (STM), visuomotor processing and attention (VSM) and abstraction/flexibility (ABS) were constructed. FE schizophrenia patients showed a worse performance compared to controls in all areas investigated, most pronounced in VSM, SEM and VBL. In the majority of cognitive domains, an improvement was found over the 5-year follow-up period without differences between the two groups. However, in VBF patients slightly deteriorated whilst controls improved and in memory functions patients improved less compared to controls. When controlling for relevant confounders, neither conventional nor atypical neuroleptics showed a deleterious influence on NP performance, except on VBF. Our data suggest that NP impairment is already present at the onset of the illness and remains stable over the early course of schizophrenia.

A prospective 2-year follow-up study of neurocognitive functioning in patients with first-episode schizophrenia.

To investigate the temporal stability, or progressivity, of neuropsychological (NP) impairment in schizophrenia, 50 patients with first episode (FE) schizophrenia and 50 healthy controls were given a battery of tests at the outset of the study and after a two-year interval. Both patient and control groups were balanced with respect to age, gender, education and parental socioeconomic status. Summary rating scales for semantic memory (SEM), visual memory (VIM), verbal learning (VBL), visual-motor processing and attention (VSM) and abstraction/flexibility (ABS) were constructed. FE schizophrenics showed improvement in VBL, stability of function in SEM, VSM and ABS and absence of improvement in VIM. While performance in VSM and VIM is influenced by medication status, SEM seems to be trait-related and stable; VBL, however, seems to be state-related. Our data suggest that there is no proof for the assumption of progressive deterioration in NP functioning during the first few years of illness.