Benzodiazepine use in the elderly: an indicator for inappropriately treated geriatric depression?

OBJECTIVE: To measure the prevalence of benzodiazepine (BZD) use and to explore associated demographic and clinical variables of BZD use within a cohort of 75-year- old inhabitants of an urban district of Vienna. METHODS: This is a prospective, interdisciplinary cohort study on aging. Our investigation is based on the first consecutive 500 subjects that completed the study protocol. Demographic and clinical characteristics, benzodiazepine and antidepressant use were documented using a standardized questionnaire. Affective status was assessed using the Hamilton Depression Rating Scale (HAMD), the Geriatric Depression Scale (GDS), and the Spielberger State-and Trait Anxiety Inventory subscales (STAI). RESULTS: Prevalence of BZD use was 13.8%. Compared to non-users, BZD users had significantly higher mean scores at the HAMD (p = 0.001), the GDS (p = 0.026), and the Spielberger State-and Trait Anxiety Inventory subscales (p = 0.003; p = 0.001). Depression was found in 12.0% (HAMD) and 17.8% when using a self-rating instrument (GDS). Less than one-third of depressed subjects were receiving antidepressants. Statistically equal numbers were using benzodiazepines. CONCLUSIONS: Inappropriate prescription of BZD is frequent in old age, probably indicating untreated depression in many cases. The implications of maltreated geriatric depression and the risks associated with benzodiazepine use highlight the medical and socioeconomic consequences of inappropriate BZD prescription.

Clonazepam in the long-term treatment of patients with unipolar depression, bipolar and schizoaffective disorder.

The value of a long-term treatment with clonazepam in the prophylaxis of affective disorder is discussed controversially in the scientific literature. Altogether there are only a few reports on the use of this compound as a mood stabilizer, most of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate clonazepam as a phase prophylactic medication in affective disorder. We conducted a retrospective chart review in 34 out-patients of our lithium clinic (15 suffering from unipolar depression, 15 from bipolar disorder, four from schizoaffective disorder), who had been treated with clonazepam as a long-term medication. Clonazepam was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients with unipolar depression had significantly (P=0.026) less depressive episodes after initiation of treatment with clonazepam. Patients with bipolar disorder did not benefit from this therapy. Neither manic/hypomanic phases nor depressive episodes were reduced in this group of patients. Interestingly, clonazepam also reduced affective phases in our four schizoaffective patients on a trend level. Our results indicate that patients with unipolar depression may benefit from a maintenance treatment with clonazepam. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials.

Quetiapine in the treatment of borderline personality disorder.

Affective dysregulation, impulsivity and cognitive-perceptual difficulties are the psychopathological nuclear dimensions of Borderline Personality Disorder (BPD). Psychopharmacological treatment may become necessary during episodes of acute decompensation in which suicidal or self-destructive behaviour erupts. Some classes of psychotropic drugs have demonstrated efficacy in diminishing symptom severity and optimising functioning, such as antidepressants, mood stabilizers, benzodiazepines, opiate antagonists and antipsychotics. Conventional antipsychotics are the best-studied psychotropic medications for BPD, but nonadherence is often due to their severe side effects. Preliminary data reveal efficacy of atypical antipsychotics in BPD. We describe the impact of the novel antipsychotic drug quetiapine on severe self-mutilation in two female patients with the diagnoses of BPD. In both cases, monotherapeutic treatment with quetiapine was well tolerated and resulted in a marked improvement of impulsive behaviour and, over time, overall level of function. Though promising, our findings have to be regarded as preliminary. Due to the overall paucity of data there still is insufficient evidence to make a strong recommendation concerning continuation and maintenance therapy with atypical antipsychotics in BPD. Thus, there is a clear need for further controlled studies to evaluate pharmacological treatment options for this disorder.

Receptor and transporter imaging studies in schizophrenia, depression, bulimia and Tourette's disorder--implications for psychopharmacology.

Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. To determine patterns of brain dysfunction and to uncover the mechanism of action of centrally active compounds we used single photon emission computerized tomography (SPECT) as well as positron emission tomography (PET) in patients diagnosed with schizophrenia, depression, bulimia and Tourette's disorder. Striatal D2 and 5-HT1A receptors were studied in schizophrenia and 5-HT transporters (5-HTT) in depression and bulimia. Patients were either drug-naïve or drug free, or we studied the influence of specifically acting compounds on receptor/transporter occupancy. We could demonstrate that atypical antipsychotics have a dose-dependent (with the exception of clozapine and quetiapine) lower striatal D2 receptor occupancy rate compared with typical neuroleptics, paralleling the more favourable extrapyramidal side effects of atypical antipsychotics. However, no association between striatal D2 receptor occupancy rates and antipsychotic efficacy has been found. The measurement of 5-HT1A receptors in drug-naïve schizophrenic patients using the in vivo PET methodology revealed an increase of cortical 5-HT1A receptor binding potential in schizophrenia. beta-CIT as a ligand for measurement of 5-HT transporter densities (5-HTT) revealed lower rates in depression compared to age- and sex-matching healthy controls, a measurement that has also been obtained for bulimia. We also documented seasonal variations in brain serotonergic function by our finding of reduced brain 5-HTT availability in winter (compared to summer) in healthy controls. Furthermore, displaceable [123I] beta-CIT binding in the area corresponding to the left striatum (representing predominantly the density of dopamine transporters) was significantly reduced in SAD patients compared to healthy controls. In depression as well as in bulimia, selective serotonin reuptake inhibitors significantly decreased the beta-CIT binding potential, however, no significant dose relationship has been obtained in depression. Genotyping depressed patients for the serotonin transporter promoter gene region (5-HTTLPR) did not provide evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects. In patients suffering from Tourette's disorder (TD) we were unable to detect differences of dopamine transporter densities between psychotropic drug-naïve TD patients and controls. Furthermore, no difference could be found between currently treated (with antipsychotics) and psychotropic drug-naïve TD patients. Our data provide insight into the pathophysiology of neuropsychiatric disorders and may guide future psychopharmacological drug developments.

[Non-extrapyramidal motor side-effects in long-term therapy with neuroleptics: an analysis of 99 patients]. / Nicht-extrapyramidalmotorische Nebenwirkungen in der Langzeittherapie mit Neuroleptika: Eine Analyse von 99 Patienten.

Compliance is the degree of adherence to medical advice. Therapeutic success, especially in long-term therapy, largely depends on the patient's compliance. Advances in psychopharmacology have led to the production of medications with substantial efficacy in the treatment of schizophrenia. The tolerability profile of these atypical antipsychotic drugs shows a lower incidence of extrapyramidal motor side effects. However, other, perhaps more trivial, side effects impair their good tolerability and may severely reduce compliance. We assessed the acceptance of these side effects in 99 patients under neuroleptic long term treatment. Difficulties to concentrate, weight gain, dizziness, vision impairment, and headache were found to be the subjectively most distressing side effects. Female patients may be at particular risk of discontinuing medication due to side effects (especially weight gain). Our results suggest that non-compliance as a clinical problem should lead to an individualized treatment, which is best developed in the context of an ongoing physician-patient relationship. Furthermore the assessment of other neuroleptic side effects besides motor disturbances seems to be of outstanding importance.

[Transcranial magnetic stimulation (TMS)--from diagnostic procedure to therapy]. / Transkranielle Magnetstimulation (TMS)--vom diagnostischen Verfahren zur Therapie.

Transcranial magnetic stimulation (TMS) has been a well-established diagnostic tool in neurological practice for many years. It has been shown to be a safe and well tolerated method. Lately this technique has also found its way to psychiatry for the treatment of mood disorders. Several studies which investigated TMS of deeper brain regions found antidepressive effects in analogy to electro convulsive therapy (ECT). This could present a significant advantage, because TMS provides non-invasive and painless stimulation of the cerebral cortex. The method is based on the principle that a time-varying magnetic field induces an electric field which leads to activation of inhibitory and excitatory neurons in neural tissue. The magnetic field pervades the intact scalp and skull without loss of energy. Both case reports as well as clinical studies have shown that TMS could present a promising option in the treatment of depression. A review of the literature demonstrates that further studies are needed to clarify many questions regarding technical and clinical aspects, such as dosage, duration of application, localization of the coils, as well as the impact of rapid-rate TMS and stronger magnetic field generators, before TMS will become an established tool in the treatment of psychiatric disorders.

Favourable results in treatment-resistant schizophrenic patients under combination of aripiprazole with clozapine.

Clozapine is still the gold standard in treatment-resistant schizophrenia. However, a substantial amount of patients do not fully recover on clozapine monotherapy. Though there is still a lack of randomised controlled studies of combination strategies in treatment-resistant schizophrenia, they are widely used. Aripiprazole is a relatively new therapeutic option due to its partial D2 agonism. Both clozapine and aripiprazole, though having a generally favourable side-effect profile, may lead to insufficient response and might provoke side effects in monotherapy. We report the case of four patients in whom we observed a distinct clinical improvement with respect to positive and negative symptoms without major side effects under a combination of clozapine and aripiprazole. The combination of clozapine action and aripiprazole-mediated D(2) receptor regulation could be responsible for the described favourable effects and for the increase of D(2) receptor blockade after adding aripiprazole to clozapine observed in one patient. A combination of clozapine and aripiprazole may be an effective therapeutic strategy for some schizophrenic patients, leading to a good response with respect to positive and negative symptoms without the occurrence of major side effects.

Diet blues: Methodological problems in comparing non-pharmacological weight management programs for patients with schizophrenia.

Obesity is an evident problem in patients with schizophrenia because it involves serious risks of health and has major effects on morbidity and mortality. Compared with the general population the prevalence of obesity is significantly increased in people with schizophrenia. Since second-generation antipsychotics have been established, the problem has become even more prevalent. Causes and treatment of obesity are both very complex issues. This article analyzes weight management programs for people with schizophrenia in regard to scientific methodology like intervention criteria, target definition and study design.