Faculty Bibliography

In this chapter we discuss the effects of moderate ethanol consumption on the treatment of psychiatric and sleep disorders. A review of the literature on the interactions of ethanol with neurotransmitters and psychotropic medications suggests that although ethanol affects the clinical course of psychiatric and sleep disorders by different mechanisms, it does so principally through perturbations it causes in the balance of central nervous system neurotransmitter systems, which may modify the clinical course of primary psychiatric and sleep disorders and undermine the therapeutic response to psychotropic medications. Neurotransmitter responses may also be manifested clinically by rebound phenomena, akin to a subsyndromal withdrawal, which affect sleep and precipitate anxiety and mood symptoms. In addition, ethanol also modifies the clearance and disposition of a variety of psychotropic metabolites and interferes with their clinical effectiveness. We recommend that most psychiatric patients, and all patients with sleep disorders, should abstain from even moderate ethanol use, as this may adversely affect their clinical course and response to treatment

Agitation is a nonspecific constellation of symptoms seen in a variety of psychiatric disorders, ranging from psychotic exacerbations in patients with schizophrenia to behavioral disturbances associated with organic factors. Its treatment must be individualized and based on the etiology of the psychomotor disturbance. Certain categories of drugs are broadly effective. Sedation and control of disruptive and dangerous behavior are the initial goals in stabilizing acutely agitated patients. Sedation is necessary during the lag period before antipsychotic and mood-stabilizing drugs take effect. Barbiturates and chlorpromazine, initially given to control agitated behavior, are largely supplanted by higher-potency antipsychotics, benzodiazepines, and, recently, a combination of these two agents. Agitation is generally controlled within hours to days, whereas remission of affective or psychotic symptoms often requires weeks to months. Once remission is obtained, sedation is no longer desired and may be a barrier to optimal patient function and compliance. Thus, for long-term treatment, strategies are used to minimize sedation, such as reducing dosages, changing administration to bedtime, or adding antidepressants or stimulants where appropriate

BACKGROUND: There is no published review to help the clinician clarify the potential role of moderate ethanol consumption in patients being treated for anxiety and mood disorders. Product labels and textbook chapters routinely warn the individual against the consumption of ethanol when using prescription psychotropic drugs. A general understanding is that the reason for this recommendation is the potential for adverse synergistic effects or sedation and decreased psychomotor performance. What is overlooked by this emphasis on safety is the effect of alcohol use both on the underlying psychiatric disorder being treated and on the effectiveness of drug therapy. METHOD: We review the available literature on the interactions of ethanol with neurotransmitters and psychotropic medications and explore the clinical consequences of these interactions. RESULTS: Ethanol might affect anxiety and mood disorders by different mechanisms. Principal among these are the effects of ethanol on multiple neurotransmitter systems, which adapt in different ways to the acute and/or chronic presence of ethanol. Perturbations in the balance of CNS neurotransmitter systems may modify the acute clinical course of primary mood disorders and undermine the therapeutic response to psychotropic medications. Ethanol also modifies the clearance and disposition of psychotropic metabolites and interferes with their clinical effectiveness. Neurotransmitter responses may additionally be manifested clinically by rebound phenomena, akin to a subsyndromal withdrawal, which affect sleep and precipitate anxiety and mood symptoms. Recent alcohol use also may alter the subjective interpretation of the patient's 'internal milieu,' causing confusion and eliciting reactive psychopathology. CONCLUSION: While much research remains to be done, there is abundant evidence that patients with mood and anxiety disorders should abstain from even moderate ethanol use, as this adversely affects their clinical course and response to treatment

To test the hypothesis that the cytochrome P-450-inhibiting antiepileptic drug (AED) stiripentol (STP) can reduce the incidence of phenytoin (PHT) induced congenital malformations, we chronically administered the AEDs to three inbred mouse strains. The frequency of congenital defects in PHT-treated animals was dosage dependent, ranging from 7 to 55%. When STP was coadministered orally with PHT, there was a significant reduction in fetal defects in SWV and C57BL/6J mouse strains. A replication of the experiment was conducted with addition of a seventh group of mice that received the high dosage of PHT together with STP. In the replicate, all three strains demonstrated a significant reduction in fetal defects in fetuses exposed to PHT (60 mg/kg) and STP (200 mg/kg) as compared with PHT (60 mg/kg) monotherapy. These results strongly suggest that oxidative metabolites activated by cytochrome P-450 are the primary teratogenic molecules involved in PHT-induced teratogenesis and that clinical management of pregnant epileptic patients may be improved through heightened awareness of these drug interactions.