Pharmacokinetics of desipramine in Caucasian and Asian volunteers.

The plasma levels of 20 healthy Asian subjects who received a single dose of desipramine were compared with those of 20 healthy Caucasian subjects who received such a dose. The groups differed significantly only in that Asian subjects had an earlier time of peak serum concentration.

Management of tardive dyskinesia: current update.

Tardive dyskinesia is now widely recognised as a neurological side effect produced in susceptible individuals by ingestion of neuroleptics. In general, the disorder tends to be late in onset, but has also been reported in a small number of individuals who have received neuroleptics for only brief periods. Much effort has been spent searching for predisposing factors, but the only consistent findings are that subjects are usually elderly (and elderly females in particular), in addition to having been exposed to neuroleptic agents. More recently, the increased finding of the presence of buccolingual facial movements in elderly populations never exposed to neuroleptics may bring out a re-evaluation of the role of these agents in the aetiology of tardive dyskinesia. Although much information on tardive dyskinesia has accrued in recent years, the precise definition, subtypes and pathophysiology remain unclear. With the development and availability of standardised rating scales, the clinical description of tardive dyskinesia has expanded from the initial buccolingual masticatory syndrome to include various abnormal movements of the fingers, arms, legs etc. Efforts have been made to distinguish withdrawal tardive dyskinesia from persistent tardive dyskinesia, but, irrespective of the classification, the disorder is in many instances reversible. However, it is impossible at present to predict the reversibility of each patient: therefore early detection of tardive dyskinesia remains an important clinical goal. Pharmacological treatments are based on the currently accepted hypothesis of dopamine receptor hypersensitivity. Selective dopamine blockers (D2) which suppress tardive dyskinesia without causing an increase in Parkinsonian symptoms are at various stages of development. Acetylcholine and gamma-aminobutyric acid (GABA) also appear to play a reciprocal role with dopamine as seen by moderate success using cholinergics and 'GABAergics'. However, there is no completely satisfactory treatment at present, indicating that prevention must be the primary aim. Above all, clinicians should carefully evaluate the indication for neuroleptic drugs, and avoid their use in conditions which may be treated with more benign drugs. A strategy for management of tardive dyskinesia is presented, and indications for withdrawing or continuing neuroleptics, the treatment of withdrawal dyskinesias and the role of experimental therapies are discussed.

Schizo-affective disorder (Schneiderian positive), manic type: a comparison with mania.

Manic patients with (N = 12) and without (N = 27) Schneiderian first rank symptoms (SFRS) were compared with regard to age, age at illness onset, presence of good prognostic signs, psychopathologic variables, treatment, and family history. The lack of group differences seen on many variables is consistent with the notion that SFRS do not define a separate schizo-affective manic subtype with differences in etiology or outcome.

Plasma drug levels and clinical response to antidepressants.

Antidepressants are a key treatment in depression. The wide interindividual differences in plasma levels of these agents were initially seen as an explanation for nonresponse and a potential major advance in treating depressive disorders. However, efforts to relate plasma levels to therapeutic outcome have, in general, been disappointing. In the few instances where such relationships have been claimed, they have been weak and useful only for specific and problematic clinical conditions.

Effect of lithium on leukocytes: a two-year follow-up.

Leukocytosis is a common finding in patients given lithium salts, but few studies have addressed the possibility of persistent leukocyte elevation during long-term lithium therapy. We followed leukocyte counts in 32 manic-depressive patients over a 1-year period and in 25 over a 2-year period of lithium therapy, after establishing prelithium leukocyte baselines. During the first few weeks, most patients showed significant increases, which persisted throughout the course of treatment. These findings indicate that lithium might play a role in the treatment of certain leukopenic conditions.

Plasma levels and therapeutic response with trimipramine treatment of endogenous depression.

In a 6-week, double-blind study involving 34 endogenously depressed patients, plasma trimipramine levels of two dosage groups, 75-mg/day and 150-mg/day, were compared with regard to clinical efficacy as determined by scores on the Hamilton Rating Scale for Depression, the Clinical Global Impressions scale, and the Zung Self-Rating Depression Scale. Both dosage levels of trimipramine produced prompt, consistent, and progressive antidepressant effects. No correlation between plasma levels and clinical efficacy was found.

Relationship between plasma desipramine levels and clinical outcome for RDC major depressive inpatients.

Depressed patients (N = 31), who met Research Diagnostic Criteria for major affective disorder-depressed, were severely ill and maintained drug-free for a 1-week period on inpatient status. They received a fixed dose (150 mg/day) of desipramine for a 4-week period with drug plasma level determination and clinical ratings performed at fixed time intervals throughout the study. Despite these rigid criteria for entrance and clinical outcome measures, no obvious relationship between plasma desipramine level and clinical outcome was found. The clinical implications of this finding are discussed.

Asian/non-Asian transcultural tricyclic antidepressant psychopharmacology: a review.

1. Transcultural psychopharmacology is a discipline that seeks to determine the relative importance of society, culture, environment, genetics, and biophysiology on the prescribing and metabolism of, and response to psychotherapeutic medications. 2. Studies and surveys comparing psychotropic medication use in Asian and non-Asian populations suggest that differences may exist in drug dosage requirements, plasma drug concentrations corresponding to therapeutic and toxic effects, and the incidence and severity of adverse drug reactions. 3. This paper reviews and critiques the published controlled studies on Asian/non-Asian transcultural tricyclic antidepressant psychopharmacology, provides guidelines for the use of psychotropic medications in Asian populations, and offers suggestions for future transcultural studies. 4. Anecdotal reports suggest that differences exist between Asian and non-Asian populations in the pharmacokinetics of tricyclic antidepressants. Controlled studies have not consistently supported this view. 5. Studies with larger sample sizes and more rigorous controls are needed to determine if such differences do, in fact, exist.

Ethnicity and antidepressant response.

Modern psychopharmacology provides us with several effective antidepressants. We are increasingly recognizing the importance of interindividual differences in plasma concentration with these drugs. Such differences are caused by genetics, and the more extreme variations result from the population classified as slow hydroxylators. We now recognize that there are also substantial racial differences in the frequency distribution of slow metabolizers. The importance of studies in this area has been underscored by anecdotal reports as well as cross-cultural surveys of prescribing patterns which indicate that antidepressant dosage requirements may differ among racial groups. This review will focus on the relatively young field of cross-cultural psychopharmacology and the efforts being made to determine the importance of society, culture, environment, genetics, and biophysiology in the prescribing and metabolism of and response to antidepressant drugs.

Transcultural psychopharmacology: present and future.

Transcultural psychopharmacology is a field that seeks to determine whether differences exist in the pharmacokinetic and pharmacodynamic handling of psychotherapeutic drugs among various ethnic groups and, where present, to determine the reasons for such variation. During the past two decades a number of studies have reported differences in the pharmacokinetics and pharmacodynamics of psychotropic medications among various ethnic groups. These variations appear to be mainly determined by genetic predisposition but can be influenced by other factors such as environment, psychosocial supports, and physicians' prescribing habits. Due to study design limitations, many questions regarding the transcultural aspects of psychotropic medications still remain unanswered. This critical review discusses the transcultural psychopharmacology of Asian versus non-Asian populations. It will also include data on tardive dyskinesia, discuss new developments, touch on the problems associated with present research in the area, and provide recommendations for designing future research studies.

Acute laryngeal dystonic reactions to neuroleptics.

Two cases of acute laryngeal dystonia (laryngospasm), a rarely reported extrapyramidal reaction to neuroleptics, occurred in a public psychiatric hospital. A review of the literature revealed only seven well-documented case reports. This article discusses the clinical significance of this rare, alarming, and probably underreported phenomenon. Factors related to recognition, prediction, and management are also discussed. The review strongly advocates immediate intravenous administration of anticholinergic drugs to relieve dystonia.

Tardive dyskinesia and abnormal tongue movements.

Forty-two subjects, 20 with and 22 without clinically diagnosed tardive dyskinesia (TD), were rated for TD on the scale of Simpson et al. They also performed a tongue protrusion test and had the presence of tongue movements within the buccal cavity observed. Fifty per cent of the severe or definite TD subjects as classified by rating scale were unable to maintain tongue protrusion for a minimum of 30 seconds, and 85 per cent of them had abnormal tongue movements. In 45 per cent of the possible TDs and in 9 per cent of the doubtful subjects, the movement test was also positive.

The treatment of refractory schizophrenia: pharmacotherapy and clinical implications of blood level measurement of neuroleptics.

The treatment of refractory schizophrenia requires careful definition. This is usually a statement based on clinical and/or intuitive experience. The definition can be extended and tightened if laboratory evidence is incorporated into this definition. Suggestions on how to accomplish this, e.g. measuring blood levels of antipsychotic agents, are made. Strategies for "trials of therapy' in nonresponsive patients and for decisions for changing to a new antipsychotic agent are presented. Clinical and laboratory difficulties in tackling this problem are also discussed.

An update on tardive dyskinesia.

The authors review recent research on definition, diagnosis, neuropathophysiology, treatment, management, and factors that increase risk of tardive dyskinesia, a severe and often unremitting movement disorder associated with neuroleptic treatment. Supersensitivity of dopamine receptors is believed to be the cause of tardive dyskinesia, and treatment strategies have consisted of pharmacologic blockade of dopamine receptors, depletion of dopamine, and restoration of the balance between the dopaminergic system and the neurotransmitter systems that regulate it. Several experimental neuroleptics that do not appear to cause tardive dyskinesia may be approved for use in the United States, but for now preventive measures, such as wise prescription and gradual tapering of neuroleptics, as well as careful monitoring for symptoms of tardive dyskinesia are the clinician's best defense.

Saliva and plasma desipramine levels in Asian and Caucasian volunteers.

Thirty-seven healthy volunteers (18 Asian, 19 Caucasian) ingested a single desipramine (DMI) dose of 1.0 mg/kg of body weight. Saliva and plasma samples were obtained at 1, 3, 5, 7, 12, 24, 48, 72, and 96 hrs after dosing. A nested repeated-measures analysis of variance (ANOVA) design was used to determine if the plasma/saliva DMI ratio varied between Asians and Caucasians over time. Regression analysis was used to assess the ability of saliva DMI to predict plasma DMI at any time point. The ANOVA results indicated no significant differences in DMI plasma/saliva ratios between Asians and Caucasians. There was a major effect of sampling time on the DMI plasma/saliva ratio (p = 0.0001), with the ratio falling from 1.78 at 1 hr to 0.15 at 96 hrs. At any given time at least 24 hrs after the dose, there was a significant relationship between saliva and plasma levels across individuals. However, across subjects, the 95 percent confidence limits for predicting plasma DMI from saliva DMI levels were relatively large. The potential roles and limitations of saliva DMI in pharmacokinetic studies and clinical drug monitoring are discussed.