Cns Drugs
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Review Comparative Study
Venlafaxine extended-release: a review of its use in the management of major depression.
Venlafaxine inhibits presynaptic reuptake of serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine). Venlafaxine extended-release (XR) has been investigated in patients with major depression and in patients with major depression with associated anxiety in randomised, double-blind, multicentre trials. A therapeutic response in patients with major depression was evident at week 2 of treatment with venlafaxine XR 75 to 225 mg/day in a placebo-controlled trial. By week 4, the drug was significantly more effective than placebo at reducing both the Hamilton Rating Scale for Depression (HAM-D) and Montgomery-Asberg Depression Rating Scale (MADRS) total scores. Furthermore, cumulative relapse rates were lower among recipients of venlafaxine XR 75 to 225 mg/day than placebo recipients after 3 and 6 months in another trial. Venlafaxine XR 75 to 150 mg/day was significantly more effective than venlafaxine immediate-release (IR) 75 to 150 mg/day or placebo during a 12-week study. Reductions from baseline in all 4 efficacy parameters (HAM-D, MADRS, HAM-D depressed mood item and the Clinical Global Impression Severity of Illness scale) were significantly higher among patients treated with venlafaxine XR than venlafaxine IR or placebo at week 12 (using an intent-to-treat, last observation carried forward analysis). Venlafaxine XR 75 to 225 mg/day was compared with fluoxetine 20 to 60 mg/day in patients with major depression in 2 randomised, double-blind, placebo-controlled, multicentre studies. Remission rates were significantly in favour of venlafaxine XR recipients in one study: 37, 22 and 18% of patients treated with venlafaxine XR, fluoxetine or placebo, respectively, achieved full remission (HAM-D total score < or = 7 at end-point). In the other trial, venlafaxine XR and fluoxetine had comparable efficacy in reducing HAM-D and Hamilton Rating Scale for Anxiety (HAM-A) total scores compared with placebo. However, the HAM-A response rate was significantly higher with venlafaxine XR than with fluoxetine at week 12. In a comparative study involving paroxetine, reductions from baseline in HAM-D and MADRS total scores in patients given venlafaxine XR 75 mg/day or paroxetine 20 mg/day for 12 weeks were significant, but no significant differences between treatment groups were evident. Discontinuation rates because of unsatisfactory clinical response were similar among patients treated with venlafaxine XR, fluoxetine or paroxetine. Adverse events pertaining to the digestive (nausea, dry mouth), nervous (dizziness, somnolence, insomnia) and urogenital (abnormal ejaculation) systems as well as sweating were the most frequently reported adverse events during 8 to 12 weeks of treatment in 3 randomised, double-blind, multicentre trials. Comparative studies with fluoxetine and paroxetine demonstrated a similar adverse event profile to venlafaxine XR. ⋯ Venlafaxine XR has shown efficacy in the treatment of major depression and was at least as effective as fluoxetine or paroxetine and more effective than venlafaxine IR. Furthermore, it is effective at reducing symptoms of anxiety in depressed patients. The incidence of adverse events in recipients of venlafaxine XR is similar to that in patients receiving treatment with well established selective serotonin reuptake inhibitors. As an effective and well tolerated antidepressant, venlafaxine XR should be considered as a first-line pharmacological treatment in patients with major depression.
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Nonconvulsive status epilepticus (SE) is not uncommon and comprises at least one-third of all cases of SE. However, nonconvulsive SE consists of very different syndromes, a common feature being the difficulty in making the diagnosis. In this review, nonconvulsive SE is divided into typical absence SE, complex partial SE, nonconvulsive SE in patients with learning difficulties (including electrical SE during sleep, atypical absence SE and tonic SE), and nonconvulsive SE in coma. ⋯ In some circumstances intravenous medication is necessary, but in neither condition is anaesthetic coma recommended. This contrasts with nonconvulsive SE in coma in which a more aggressive approach is suggested. Until there are more relevant animal models, and controlled trials of conservative versus more aggressive treatment, treatment regimens for nonconvulsive SE will remain largely speculative.
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An intrinsic body clock residing in the suprachiasmatic nucleus (SCN) within the brain regulates a complex series of rhythms in humans, including sleep/wakefulness. The individual period of the endogenous clock is usually >24 hours and is normally entrained to match the environmental rhythm. Misalignment of the circadian clock with the environmental cycle may result in sleep disorders. ⋯ Melatonin replacement therapy may also provide a rational approach to the treatment of age-related insomnia in the elderly. However, there is currently no melatonin formulation approved for clinical use, neither are there consensus protocols for light or melatonin therapies. The use of bright light or melatonin for circadian rhythm sleep disorders is thus considered exploratory at this stage.
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Perospirone is an atypical antipsychotic agent for the treatment of schizophrenia. Its primary mode of action is through antagonism of serotonin 5-HT2A and dopamine D2 receptors. An 8-week course of oral perospirone 8 to 48 mg/day displayed efficacy in up to 75% of patients with schizophrenia participating in phase II and phase III trials. ⋯ Compared with haloperidol 2 to 12 mg/day, perospirone 8 to 48 mg/day was significantly more effective against negative symptoms and tended to be more effective against general symptoms and most positive symptoms in a trial in 145 patients with schizophrenia. Perospirone had efficacy similar to that of mosapramine 50 to 300 mg/day in a comparative phase III trial in 159 patients. Extrapyramidal symptoms (EPS) tended to occur less often and were generally milder with perospirone than with haloperidol or mosapramine.
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Stiff man syndrome (SMS), an uncommon neurological disease, is characterised by symmetrical muscle stiffness and spasms that often lead to skeletal deformity. Variants of the syndrome may involve one limb only (stiff leg syndrome), a variety of additional neurological symptoms and signs such as eye movement disturbances, ataxia, or Babinski signs (progressive encephalomyelitis with rigidity and myoclonus), or be associated with malignant disease (paraneoplastic SMS). Antineuronal autoimmunity and accompanying autoimmune diseases, most often insulin-dependent diabetes mellitus, are characteristic features of SMS and its variants. ⋯ Plasmapheresis or intravenous immunoglobulins are effective less frequently. For symptomatic treatment, the benzodiazepines are drugs of first choice. An alternative of last resort is baclofen administered intrathecally via an implanted pump device.