Cns Drugs
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Great progress has been made in the last 150 years in the pharmacological management of epilepsy, and, despite the increasing number of technological advances available, antiepileptic drugs (AEDs) remain the mainstay of treatment for the vast majority of patients with epilepsy. This review looks at possible avenues of development in the drug treatment of epilepsy. The strengths and weaknesses of those AEDs which are currently licensed are examined, and ways in which their use may be improved are discussed (e.g. rational combinations, use of new formulations). Potentially new targets that may allow the development of effective treatments are highlighted (neuroimmunological manipulation, decreasing inherent drug resistance mechanisms, and modification of adenosine neurotransmission), and a summary of the most promising AEDs currently in development is provided [e.g. carabersat, ganaxolone, harkoseride, MDL 27192, safinamide (NW 1015), pregabalin, retigabine, talampanel, valrocemide, losigamone and BIA 2093].
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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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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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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.