Benzodiazepines present problems related to both unwanted and withdrawal effects. Dosage adjustments usually obviate unwanted effects except for paradoxical reactions such as hostility. Patients with apparent benzodiazepine dependence need careful assessment with respect to personality, social situation and psychiatric disorder. The patient must be motivated and carefully prepared for withdrawal and taught anxiety management techniques. Withdrawal must always be gradual over at least 6 weeks but very prolonged schedules are counter-productive. Substituting a long-acting for a medium-acting benzodiazepine may be helpful in the more intractable cases. An antidepressant may be needed if a depressive disorder supervenes, but other adjunctive therapies are usually unhelpful.
Schizotypy is taxonic and schizotypy class membership is predicted by genetic and environmental factors that predict schizophrenia. The findings hold the promise that a more complete understanding of schizotypy as a schizophrenia liability state will come from investigation of other genes and environmental factors associated with schizophrenia.
The potential of the benzodiazepine antagonist flumazenil (Ro 15-1788) to lessen persisting benzodiazepine withdrawal symptoms was demonstrated in 11 patients who had been drug free for between 1 month and 5 years. Doses ranging from 0.2 to 2.0 mg divided into three intravenous injections over a few hours relieved long-standing symptoms to varying extents. These included clouded thinking, tiredness, muscular symptoms such as neck tension, cramps and shaking and the characteristic perceptual symptoms of benzodiazepine withdrawal, namely, pins and needles, burning skin, pain and subjective sensations of bodily distortion. Mood disorder, when present, also improved but the reduction in anxiety and depression may have reflected relief of physical symptoms. The onset of maximum response was sometimes delayed by as much as a day but was usually prompt. Side effects were reported to be either absent or typically described as lightheadedness or dizziness, lasted only a few minutes and were usually well tolerated. The benefits last between a few hours and several days despite flumazenil's otherwise short duration of action. However, symptoms did return to varying degrees in most cases, suggesting the need for repeated doses.
If schizotypy is a taxonic liability for schizophrenia with a general population prevalence of ~10%, it should also be taxonic among biological siblings of probands with schizophrenia. Moreover, assuming this is so, siblings' schizotypy class membership should be predicted by probands' familial load for psychotic disorder and clinical severity, consistent with a multifactorial polygenic threshold model of schizophrenia. We tested these hypotheses in the Genetic Risk and Outcome of Psychosis (GROUP) Study where siblings of probands (n = 792) and unaffected controls (n = 559) provided self-report ratings on the Community Assessment of Psychic Experiences (CAPE). Maximum covariance analyses of control group ratings led to the identification of CAPE items sensitive to nonredundant positive and negative schizotypy classes in the control group (prevalence = 7.9% and 11.1%, respectively). When the same taxonic solution was applied to siblings' CAPE rating, taxometric analyses yielded evidence for larger positive and negative schizotypy classes among siblings (prevalence = 14.1% and 21.8%, respectively). Whereas probands' familial loads for bipolar disorder or drug use disorders did not predict siblings' membership in the schizotypy classes, probands' familial load for psychotic disorder did. Siblings were more likely to be members of the positive schizotypy class where their probands were more severely affected. The pattern of findings is consistent with Meehl's argument that schizotypy reflects liability for schizophrenia.
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