Quetiapine dosage in bipolar disorder episodes and mixed states

OBJECTIVE: Although the maximal quetiapine doses in the published studies were restricted to 800 mg/day, higher quetiapine doses are not unusual in clinical practice. The aim of the present study was to evaluate the effectiveness, tolerability and clinical reasons associated to the use of high dosage of quetiapine (>800 mg), when used under routine clinical conditions, in a sample of bipolar disorder and schizoaffective bipolar inpatients. METHODS: Charts of all bipolar and schizoaffective adult inpatients, who had received quetiapine for a mood episode between 1999 and 2005 were retrospectively reviewed. These charts also included the assessment of manic and depressive symptoms on admission and at discharge using the Beck-Rafaelsen Mania Scale (MAS) and the Montgomery Asberg depression rating scale (MADRS), respectively. RESULTS: Data of 50 patients were analyzed. The overall F in repeated measures ANOVA revealed a significant MAS scores reduction between admission and discharge. MAS scores reduction did not differ between the high and low quetiapine groups. Similarly, a significant MADRS reduction was found. Again, no differences between the high and the low dose group were found. Logistic regression analysis of the 50 patients revealed only mixed episodes predicted high quetiapine dosage. CONCLUSIONS: The present study confirms quetiapine efficiency and tolerability in the treatment of bipolar episodes, even in doses > to 800 mg and found a link between quetiapine doses and mixed episodes.     

The Montgomery Asberg Depression Rating Scale in bipolar II and unipolar out-patients: A 405-patient case study

The aim of the present study was to find if the Montgomery Asberg Depression Rating Scale (MADRS) can identify symptom differences between bipolar II and unipolar depression. Four hundred and five consecutive bipolar II and unipolar depressed out-patients were interviewed with the Comprehensive Assessment of Symptoms and History structured interview, following DSM-IV criteria, the MADRS, and the Global Assessment of Functioning Scale. The Montgomery Asberg Depression Rating Scale items were not significantly different between bipolar II and unipolar patients. Comparisons among atypical and non-atypical bipolar II and unipolar patients showed that only MADRS items of 'reduced sleep' and 'reduced appetite' were significantly different between atypical and non-atypical patients.     

Combined antipsychotic treatment involving clozapine and aripiprazole

Treatment resistance is considered a challenging problem of antipsychotic pharmacotherapy. In such cases, combination approaches are commonly used, for instance the add-on of aripiprazole to clozapine. This review aims at giving an overview of the present knowledge on this strategy. We performed a keyword-based screening of databases (including November 2007) and evaluated the data in a systematic manner. The courses of 94 patients were reported in 11 publications. At a mean dosage of 20.5 mg/day, aripiprazole achieved clinical improvement of psychotic symptoms and facilitated a dose reduction of clozapine from 476.7 to 425.1 mg/day. In parallel, clozapine serum levels decreased from 611 to 523 ng/ml. No pharmacokinetic interactions were reported, and clozapine-induced side effects ameliorated. However, single cases of extrapyramidal side effects occurred. The combination of clozapine and aripiprazole follows a neurobiological rationale and appears to be effective and tolerable. The results of placebo-controlled trials might allow further insight into the benefits and risks of this strategy.     

Association of the STin2 polymorphism of the serotonin transporter gene with a neurocognitive endophenotype in major depressive disorder

BACKGROUND:: The aim of our study was to investigate the association of STin2 polymorphism and cognitive dysfunction in major depression. METHODS:: 71 patients with major depression and 99 controls were genotyped for STin2. All depressive subjects and 30 controls also completed tests measuring neurocognitive performance. RESULTS:: We found a significantly higher frequency of the STin2.10/Stin2.10 homozygous genotype in the depressed group compared to controls. In the depressed group subjects with at least one copy of the 10-repeat allele showed decreased interference threshold in Stroop III compared to patients without the 10-repeat allele. Average performance of the depressed group without the 12-repeat allele was significantly weaker in the Rey Auditory Verbal Learning Test working memory and recall tasks compared to patients having at least one copy of the 12-repeat allele. CONCLUSION:: Our results suggest that the presence of STin2.10 and absence of STin2.12 allele may be related to a possible genetic endophenotype for characteristic cognitive dysfunctions detected in MDD.     

Prediction of relapse in melancholic depressive patients in a 2-year follow-up study with corticotropin releasing factor test

Purpose

To study the power of CRF stimulation test to predict relapse in a sample of melancholic depressive patients in depressed phase, followed-up over a two-year period from the moment they achieved complete remission of depressive symptoms.

Methods

Fifty-one outpatients diagnosed with unipolar depressive disorder with melancholic features according to DSM-IV were assessed with the CRF test. The Structured Clinical Interview for DSM-IV (SCID-IV) was used for diagnosis. Monthly follow-up visits were held over a two-year period after remission; relapse was established using HDRS according to Frank's criteria [Frank E, Prien RF, Jarret RB, Keller MB, Kupfer DJ, Lavori PW, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder: remission, recovery, relapse, and recurrence. Arch Gen Psychiatry 1991;48:851–5]. Forty-three patients completed the study. Non-controlled antidepressant treatment protocols were used. Predictive statistical analysis was performed through logistic regression.

Findings

The final predictive model included three variables: net area under cortisol curve (NAUCC), previous suicide attempt, and stress during follow-up. Sensitivity was of 89%, and specificity was of 92%. NAUCC has shown a predictive power of 80%, with an optimal cut-off point of 251.24 μg/ml/min.

Conclusions

Cortisol is the hormone of the HPA axis which shows the highest power to predict relapse. NAUCC is the most relevant variable. The complete predictive model is a complex combination of biological, clinical and psychoenvironmental variables (NAUCC, previous suicide attempts, and stress during follow-up). Further studies with better control of the psychoenvironmental variables are required to obtain more precise neuroendocrine findings.     

Augmentation of antidepressants with perospirone for treatment-resistant major depressive disorder

We examined the efficacy and tolerability of perospirone, a dopamine D2 and 5-HT2A receptor antagonist and a partial 5-HT1A receptor agonist, in the augmentation of antidepressant treatment of partially responding and nonresponding patients with major depressive disorder. Twelve patients with major depressive disorder and an incomplete or no response to different kinds of antidepressants (selective serotonin reuptake inhibitor, milnacipran, or sulpride) monotherapy or polytherapy for 8 weeks or more were treated with perospirone augmentation in an eight-week, open-label study. Data were gathered from July 2006 to March 2008. The mean duration of antidepressant pharmacotherapy at baseline was 28 weeks. At baseline, the mean (± SD) of the MADRS scores was 35.8 ± 10.1. The mean (± SD) initial dose of perospirone was 7.0 ± 2.9 mg/day and the final dose was 11.7 ± 6.6 mg/day. Significant reductions in MADRS scores were observed at weeks 2, 4, 6 and 8. Although two of the twelve subjects who completed the protocol achieved remission by the study endpoint, five of the twelve patients were responders (i.e., > 50% improvement in the MADRS score). Sleepiness and tremor were observed in six patients and one patient, respectively, resulting in a reduction of perospirone dose due to these side effects. The discontinuation rate after 8 weeks of treatment was zero. These findings suggest that perospirone may be an effective augmentation strategy for improving therapeutic response in patients with treatment-resistant major depressive disorder when administered in combination with standard antidepressant therapy. Based on this clinical evidence, a double-blind, placebo-controlled trial is warranted.     

Coping and quality of life of patients with Parkinson disease who have undergone deep brain stimulation of the subthalamic nucleus

Background

Although the positive effect of DBS of the STN on motor signs and mobility in PD is indisputable, the effect on mental health (depression and anxiety) as well as on QoL is subject to more debate. Some works have already shown that coping strategies have an impact on QoL, depression, and anxiety. To date, no studies have examined the coping strategies used by patients with PD who undergo STN stimulation. We decided to investigate the coping strategies of patients with PD who have undergone an STN DBS and their relationship with QoL while taking depression and anxiety into account.

Methods

A total of 40 patients stimulated for 12 months and 40 patients under dopatherapy were compared. The 2 groups were matched according to age, sex, age at disease onset, severity of disease, motor scores, daily treatment dosage, and professional status. Semistructured interviews were carried out, after which, their mental and cognitive states were assessed using different scales (MINI, MADRS, EHD, HAMA, FAB). Finally, all subjects completed 3 self-report questionnaires: 2 assessing coping strategies (WCC, CHIP), and 1, QoL the Parkinson Disease Questionnaire (PDQ-39).

Results

Depression and anxiety were not significantly influenced by the type of treatment. Concerning coping strategies, we found a significant effect of the stimulation on instrumental strategies with higher scores for patients under dopatherapy. As for QoL, the only difference concerned communication with a poorer QoL for stimulated patients. We noted no significant correlations between any coping strategies and all of the dimensions of QoL in the stimulated group, whereas we found the opposite result for the dopatherapy group.

Conclusions

These results encourage us to prepare patient candidates for such stimulation by developing interventions focused first on their expectations and second, on their coping strategies.     

A monoamine oxidase B gene variant and short-term antidepressant treatment response

Genetic differences among patients suffering from Major Depression are likely to contribute to interindividual differences in medication treatment response. Thus, the identification of gene variants affecting drug response is needed in order to be able to predict response to psychopharmacological drugs. This study analyzed a possible association of the common A644G single nucleotide polymorphism (SNP) within intron 13 of the monoamine oxidase B (MAOB) gene with antidepressant treatment response. The study population consisted of n = 102 patients with major depression (criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; DSM-IV) participating in a randomized double-blind controlled clinical trial, conducted at 50 centers in Germany, comparing the efficacy of mirtazapine and paroxetine during 6 weeks of treatment. Overall, female patients homozygous for the A-allele had a significantly faster and more pronounced antidepressant treatment response than AG/GG-carriers. In paroxetine-treated females these differences remained statistically significant. In mirtazapine-treated females homozygous for the A-allele compared to AG/GG-carriers, HAMD-17 scores during the study period were constantly and markedly lower, but not statistically different. In males, we found no association between the MAOB A644G intron 13 SNP and antidepressant treatment response. Our data provide first suggestive evidence that the MAOB A644G SNP is involved in the outcome of treatment with mirtazapine or paroxetine in females with major depression. To confirm the role of the MAOB A644G gene variant in antidepressant treatment response, independent replications are needed. If replicated, the MAOB A644G polymorphism could be considered useful for prospective confirmatory pharmacogenetic trials in patients with major depression.     

Brain GABA levels in patients with bipolar disorder

Purpose

A growing body of research supports an important role for GABA in the pathophysiology of bipolar and other mood disorders. The purpose of the current study was to directly examine brain GABA levels in a clinical sample of bipolar patients.

General methods

We used magnetic resonance spectroscopy (MRS) to examine whole brain and regional GABA, glutamate and glutamine in 13 patients with bipolar disorder compared to a matched group of 11 healthy controls.

Findings

There were no significant differences in GABA, glutamate or glutamine between patients and controls.

Conclusions

Further research is needed to better characterize the GABAergic and glutamatergic effects of pharmacotherapy, anxiety comorbidity and clinical state in bipolar disorder.