Subject withdrawal periods

The potential interaction of paroxetine 20 mg/day and alprazolam 1 mg/day for 15 days on polysomnographic sleep and subjective sleep and awakening quality has been evaluated in a randomized, double-blind, doubledummy, placebo-controlled, repeated-dose, four-period, crossover study in 22 young subjects with no history of sleep disturbances (29). There were subjective withdrawal symptoms after abrupt discontinuation of alprazolam, including increased subjective sleep latency and reduced subjective sleep efficiency. 

Perhaps the most obvious method of studying kinetic systems is to periodically withdraw samples from the system and to subject them to chemical analysis. When the sample is withdrawn, however, one is immediately faced with a problem. The reaction will proceed just as well in the test sample as it will in the original reaction medium. Since the analysis will require a certain amount of time, regardless of the technique used, it is evident that if one is to obtain a true measurement of the system composition at the time the sample was taken, the reaction must somehow be quenched or inhibited at the moment the sample is taken. The quenching process may involve sudden cooling to stop the reaction, or it may consist of elimination of one of the reactants. In the latter case, the concentration of a reactant may be reduced rapidly by precipitation or by fast quantitative reaction with another material that is added to the sample mixture. This material may then be back-titrated. For example, reactions between iodine and various reducing agents can be quenched by addition of a suitably buffered arsenite solution. 

The rate of reversibility of tardive dyskinesia after drug withdrawal is 0-90% (269). Since patients with tardive dyskinesia rarely have subjective complaints (304), periodic assessment of dyskinetic movements is essential in making an early diagnosis and can increase the chance of reversing the disorder. Some reports are relatively encouraging regarding reversibility (305,306) the characteristics of reversible and irreversible forms have been reviewed, but no firm conclusion can be drawn (307). However, the prognosis of tardive dyskinesia was better in patients treated for a shorter duration and in those treated with lower doses (308). 

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