Benzodiazepine Withdrawal In Patients Research Articles

Neurocognitive performance, subjective well-being, and psychosocial functioning after benzodiazepine withdrawal in patients with schizophrenia or bipolar disorder: a randomized clinical trial of add-on melatonin versus placebo.

Chronic benzodiazepine use is common in patients with mental illness and is associated with cognitive impairment. It is unclear whether benzodiazepine-induced cognitive impairment is reversible. Amelioration of cognitive dysfunction may be facilitated during benzodiazepine tapering by add-on melatonin due to its anti-inflammatory and neuroprotective properties. We examined how melatonin and benzodiazepine withdrawal affect cognition, subjective well-being, and psychosocial functioning. Eighty patients with schizophrenia or bipolar disorder were randomized to add-on treatment once daily with either prolonged-release melatonin or placebo in a 24-week, double-blind clinical trial. All participants gradually tapered usual benzodiazepine dosage in a closely monitored treatment setting. We used the Brief Assessment of Cognition in Schizophrenia (BACS) to assess neurocognitive performance with additional assessments of subjective well-being and psychosocial functioning. BACS composite and subscale scores (except motor speed) significantly improved in parallel with benzodiazepine dose reduction, but there was no additional effect of melatonin. Cognitive performance was still markedly impaired post-tapering compared with normative data. Neither benzodiazepine withdrawal nor treatment group affected subjective well-being or psychosocial functioning. In conclusion, add-on melatonin does not seem to affect cognition, well-being, or psychosocial functioning in patients with severe mental illness. The observed improvement in cognitive performance could not be distinguished from retest effects, which may in turn have been facilitated by the benzodiazepine tapering.

BDNF plasma levels decrease during benzodiazepine withdrawal in patients suffering from comorbidity of depressive disorder and benzodiazepine dependence

Rationale Alterations in the expression of neurotrophic growth factors like brain-derived neuronal factor (BDNF) and glial cell line-derived neuronal growth factor (GDNF) have been frequently associated with affective disorders. Indeed, benzodiazepine dependence is typically combined with affective disorders. Aim of the study was to investigate plasma levels of the neuronal growth factors BDNF and GDNF during benzodiazepine withdrawal in patients suffering from comorbidity of benzodiazepine dependence and depressive disorder.

Sevrage aux benzodiazépines des sujets dépendants aux opiacés en traitement de substitution

Benzodiazepines are the most widely used psychotropic agents in the world. Abuse and dependence are reported in the general population and among drug misusers, including those dependent on heroine. Benzodiazepine use by heroine users increases their risk of overdose, not only from heroin but also substitution drugs such as methadone and more recently buprenorphine. Hence, detoxification from benzodiazepines is desirable. The objective of this paper was to review the literature and determine the best benzodiazepine detoxification procedure for opiate-dependent individuals receiving substitution treatment. Relevant studies were sought through systematic searches of Medline and Toxibase (a database focusing on substance abuse). There were fewer controlled studies than expected about benzodiazepine detoxification, and all of them excluded subjects who misused opiates or were in opiate substitution treatment. The best evidence supports a procedure where the patient is switched to a long-lasting benzodiazepine and the dose then tapered by 25% of the initial dose each week. Diazepam is the drug most often used in the framework. In opiate users, diazepam may raise special problems of misuse, as suggested by clinical and epidemiologic studies. Nonetheless, diazepam is the only benzodiazepine found to be effective for this withdrawal in controlled studies and some studies indicate that unprescribed diazepam use in heroin users is sometimes motivated by the desire to alleviate withdrawal symptoms and discomfort. Although diazepam appears to have potential for abuse, the available data does not rule out its therapeutic interest for benzodiazepine withdrawal in patients on opiate substitution treatment in an adequate treatment setting. Specific studies of this population are needed.

Impaired hypothalamic-pituitary-adrenocortical (HPA) system is related to severity of benzodiazepine withdrawal in patients with depression

A concatenation of data indicates that the pathogenesis of depression is related to an increased production and secretion of corticotropin-releasing hormone (CRH). Benzodiazepines profoundly suppress the basal and stress-related activation of the hypothalamic-pituitary-adrenocortical (HPA) system and discontinuation of these drugs results in rebound activation. We therefore investigated whether the extent of HPA system dysregulation is related to the severity of benzodiazepine withdrawal in patients with depression. We performed the combined dexamethasone/CRH test before benzodiazepine discontinuation (taper-off max. 5 mg diazepam-equivalents/week) in 14 depressed patients (13 f, 1 m, mean age 54.6 +/- 14.6) who responded to the antidepressant treatment. The severity of withdrawal symptoms was measured using the Clinical Institute Withdrawal Assessment-Benzodiazepines (CIWA-B) questionnaire. The depressive psychopathology was monitored using the Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale and Beck Depression Inventory. Patients with more severe benzodiazepine withdrawal (CIWA-B-increase > 14 pts; n = 7) showed a significant higher cortisol and ACTH response in the dexamethasone/CRH test preceding the discontinuation of benzodiazepines than patients displaying less severe withdrawal symptoms (CIWA-B-increase <14 pts.; n = 7) (ANCOVA, p < 0.05). Both groups did not differ in the pre-taper psychopathology ratings and their basal neuroendocrine activity. In view of the GABAergic inhibition of HPA system activity and the anxiogenic effect of CRH, benzodiazepine withdrawal symptoms may be partly due to a disinhibition of the HPA system during discontinuation of benzodiazepines.

Impaired hypothalamic-pituitary-adrenocortical (HPA) system is related to severity of benzodiazepine withdrawal in patients with depression

A concatenation of data indicates that the pathogenesis of depression is related to an increased production and secretion of corticotropin-releasing hormone (CRH). Benzodiazepines profoundly suppress the basal and stress-related activation of the hypothalamic-pituitary-adrenocortical (HPA) system and discontinuation of these drugs results in rebound activation. We therefore investigated whether the extent of HPA system dysregulation is related to the severity of benzodiazepine withdrawal in patients with depression. We performed the combined dexamethasone/CRH test before benzodiazepine discontinuation (taper-off max. 5 mg diazepam-equivalents/week) in 14 depressed patients (13 f, 1 m, mean age 54.6 ± 14.6) who responded to the antidepressant treatment. The severity of withdrawal symptoms was measured using the Clinical Institute Withdrawal Assessment-Benzodiazepines (CIWA-B) questionnaire. The depressive psychopathology was monitored using the Hamilton Depression Rating Scale, Montgomery Asberg Depression Rating Scale and Beck Depression Inventory. Patients with more severe benzodiazepine withdrawal (CIWA-B-increase > 14 pts.; n=7) showed a significant higher cortisol and ACTH response in the dexamethasone/CRH test preceding the discontinuation of benzodiazepines than patients displaying less severe withdrawal symptoms (CIWA-B-increase <14 pts.; n = 7) (ANCOVA, p < 0.05). Both groups did not differ in the pre-taper psychopathology ratings and their basal neuroendocrine activity. In view of the GABAergic inhibition of HPA system activity and the anxiogenic effect of CRH, benzodiazepine withdrawal symptoms may be partly due to a disinhibition of the HPA system during discontinuation of benzodiazepines.