[Prevention and Treatment of Antipsychotic-induced Tardive Dyskinesia]. / Prävention und Behandlung von Antipsychotika-induzierten tardiven Dyskinesien.

Tardive dyskinesias (TDs) are still common long-term sequelae of antipsychotic treatment. They are generally irreversible and associated with cognitive deficits, a decrease in quality of life and increased mortality. Furthermore, they potentially contribute to further stigmatization of the affected patients. However due to limited treatment options, antipsychotic drugs are still one of the cornerstones in treatment of most severe mental illnesses. Therefore, knowledge about risk factors and prevention of TDs is crucial. If TDs occur, the immediate optimization of the antipsychotic drug regimen is required. Targeted medical treatments such as VMAT - 2 inhibitors can be considered. The novel VMAT-2 inhibitors are not yet approved in Germany. Other drugs that are currently used to treat TDs include clonazepam and gingko biloba. This review summarizes the current evidence of treatment options of TDs and seeks to formulate clinical recommendations for the prevention and management of TDs.

[Diphenhydramine addiction and detoxification. A systematic review and case report]. / Diphenhydramin-Abhängigkeit und -Entzug.

OBJECTIVE: In many countries diphenhydramine (DPH) is commonly available over the counter, frequently used, and generally regarded as a harmless drug. It is used as a sedative, antiallergic or antiemetic substance. METHODS: We present a systematic review of literature search in Pubmed from 1972 to 2012 describing DPH addiction. The literature search in reveals that the addictive potential of DPH can be regarded as proved, based on cases series, eight case reports, a pharmacological overview, one uncontrolled, and one randomized, placebo controlled study. In addition we report a case of an abstinent alcoholic patient treated in our department for DPH-dependency. CONCLUSION: Especially when treating patients with a history of addiction, physicians should consider and check the possibility of a DPH dependency.

Acute antidepressive efficacy of lithium monotherapy, not citalopram, depends on recurrent course of depression.

Studies of the 1970s and 1980s showed lithium monotherapy to be an effective treatment of acute unipolar major depressive disorder (MDD) and hence as a potential alternative to monoaminergic antidepressants.The objective was to conduct the first comparison of a lithium monotherapy with a modern antidepressant in the acute treatment of MDD. Results were compared with citalopram's efficacy as shown in a different but methodologically identical study (including same researchers, same time, and same place).Thirty patients with an acute MDD (Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM IV] I) were treated with lithium monotherapy (study 1) or with citalopram monotherapy (study 2, N = 32) for 4 weeks.Response rates (decrease in Hamilton Depression Rating Scale score >50%) were 50% for lithium and 72% for citalopram (P = 0.12). Citalopram-treated subjects showed a greater decrease in Hamilton Depression Rating Scale scores (significant at 2 weeks). In the lithium study, only patients with a recurrent episode (DSM-IV: 296.3) responded (15/22), as opposed to none of 8 patients with a first/single episode (DSM-IV: 296.2) (P = 0.002). Patients with a single episode responded significantly more often to citalopram than to lithium (P = 0.007). Both drugs were well tolerated. Only one patient (citalopram) terminated the study prematurely owing to adverse effects.Our results do not support the use of lithium as an alternative to SSRI in the treatment of acute MDD. The finding of a better response to lithium in patients with a recurrent depression has not been reported before and warrants replication. The comparison is limited by the lack of a randomized double-blind design.

[Augmentation of antidepressants with atypical antipsychotics in non-delusional unipolar depressed patients with non-response to antidepressant-monotherapy]. / Augmentation von Antidepressiva mit atypischen Antipsychotika bei Nonresponse auf eine Antidepressiva-Monotherapie.

Objective Augmentation of antidepressants with atypical antipsychotics is used in depressive patients with non-response to antidepressants. We investigated the utility of this strategy.Methods Systematic computer-based search in the online library Pubmed for randomized placebo-controlled double-blind trials (RCT) from the years 1990 to 2011.Results We found 14 RCT about augmentation of antidepressants with atypical antipsychotics in depressive patients with non-response to antidepressants. Trials examined olanzapine, risperidone, quetiapine and aripiprazole.Conclusions Augmentation of antidepressants with atypical antipsychotics is an alternative to the augmentation with lithium in unipolar depressive patients with non-response to antidepressants. But treatment with atypical antipsychotics as opposed to placebo increases the risk of non-compliance due to side-effects of medication. Augmentation of antidepressants with atypical antipsychotics in unipolar depression is an off-label therapy in Germany except for the augmentation with extended-release quetiapine. Knowledge about treatment strategies regarding augmentation of antidepressants with atypical antipsychotics can increase the chance of a successful treatment, but interactions and side-effects should be considered.

Impact of citalopram on the HPA system. A study of the combined DEX/CRH test in 30 unipolar depressed patients.

BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) system is one of the best replicated pathophysiological findings in depression. However, studies on the influence of treatment on the HPA system have partly yielded inconsistent results. OBJECTIVE: To assess the effects of citalopram monotherapy on the HPA system of mainly drug naïve patients with major depression by means of the combined DEX/CRH test. METHODS: The DEX/CRH test was conducted twice in 30 patients (25 drug naïve for the index episode) with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed): directly before the start of a citalopram monotherapy (day 0) and four weeks thereafter (day 28). RESULTS: Twenty-three patients responded (≥50% reduction in the HDRS(21)-score), and 17 of them also reached criteria of remission (HDRS ≤ 7). Baseline (dexamethasone-suppressed) and CRH-stimulated ACTH concentrations significantly decreased from day 0 to day 28. CRH-stimulated cortisol concentrations also fell, although not significantly, but baseline cortisol concentrations exhibited a significant increase from day 0 to day 28. CONCLUSIONS: The blunting of the ACTH response in the DEX/CRH test under citalopram is in line with what has been observed in most studies with antidepressants. However, the partial rise in cortisol concentrations indicates an increase in the sensitivity of the adrenal cortex to ACTH. State-dependent alterations in the volume and the ACTH responsiveness of the adrenal gland have repeatedly been reported in depressed subjects, which indicates the possibility that SSRIs such as citalopram might exhibit a direct or indirect effect on the adrenal cortex.

Lithium monotherapy increases ACTH and cortisol response in the DEX/CRH test in unipolar depressed subjects. A study with 30 treatment-naive patients.

BACKGROUND: Distorted activity of the hypothalamic-pituitary-adrenocortical (HPA) system is one of the most robustly documented biological abnormalities in major depression. Lithium is central to the treatment of affective disorders, but little is known about its effects on the HPA system of depressed subjects. OBJECTIVE: To assess the effects of lithium monotherapy on the HPA system of patients with major depression by means of the combined DEX/CRH test. METHOD: Thirty drug-naive outpatients with major depression (single episode or unipolar recurrent; SCID I- and II-confirmed) were treated with lithium monotherapy for four weeks. The DEX/CRH test was conducted directly before intake of the first lithium tablet and four weeks thereafter. Weekly ratings with the HDRS(21) were used to determine response (≥50% symptom reduction) and remission (HDRS ≤7). RESULTS: Lithium levels within the therapeutic range were achieved rapidly. Tolerability was good; no patient terminated the treatment prematurely. Response and remission rates were 50% and 33% respectively. Compared to the DEX/CRH test before the start of the treatment, a considerable and significant increase in all CRH-stimulated ACTH and cortisol parameters could be detected in the second DEX/CRH test. When analysed with particular regard to responders and non-responders, that significant increase was only present in the responders. CONCLUSIONS: We were able to demonstrate that lithium leads to a significant activation of the HPA system. This is possibly connected to stimulation of hypothalamic arginine vasoporessin (AVP), to direct intracellular effects of lithium on pituitary cells and to an induction of gene expression. TRIAL REGISTRATION: drks-nue.uniklinik-freiburg.de DRKS00003185.