Joseph M. Pierre

Extrapyramidal symptoms with atypical antipsychotics : Incidence, prevention and management

The treatment of schizophrenia changed drastically with the discovery of antipsychotic medications in the 1950s, the release of clozapine in the US in 1989 and the subsequent development of the atypical or novel antipsychotics. These newer medications differ from their conventional counterparts, primarily based on their reduced risk of extrapyramidal symptoms (EPS). EPS can be categorised as acute (dystonia, akathisia and parkinsonism) and tardive (tardive dyskinesia and tardive dystonia) syndromes. They are thought to have a significant impact on subjective tolerability and adherence with antipsychotic therapy in addition to impacting function. Unlike conventional antipsychotic medications, atypical antipsychotics have a significantly diminished risk of inducing acute EPS at recommended dose ranges. These drugs may also have a reduced risk of causing tardive dyskinesia and in some cases may have the ability to suppress pre-existing tardive dyskinesia.This paper reviews the available evidence regarding the incidence of acute EPS and tardive syndromes with atypical antipsychotic therapy. Estimates of incidence are subject to several confounds, including differing methods for detection and diagnosis of EPS, pretreatment effects and issues surrounding the administration of antipsychotic medications. The treatment of acute EPS and tardive dyskinesia now includes atypical antipsychotic therapy itself, although other adjunctive strategies such as antioxidants have also shown promise in preliminary trials.The use of atypical antipsychotics as first line therapy for the treatment of schizophrenia is based largely on their reduced risk of EPS compared with conventional antipsychotics. Nevertheless, EPS with these drugs can occur, particularly when prescribed at high doses. The EPS advantages offered by the atypical antipsychotics must be balanced against other important adverse effects, such as weight gain and diabetes mellitus, now known to be associated with these drugs.

Lack of insight in schizophrenia: impact on treatment adherence.

People with schizophrenia commonly lack insight, that is, they are unaware of their illness and the consequences thereof. One of the most important consequences of lack of insight is a failure to recognise the need for treatment, leading to treatment nonadherence. With several scales that now enable objective measurement of insight, it is possible to examine correlates of insight change, including course of illness and treatment adherence. Specific interventions, both pharmacological and psychotherapeutic, have been developed to enhance illness insight and treatment adherence. The extent to which second-generation antipsychotic medications, including a recently released long-acting formulation, improve insight and/or enhance treatment adherence remains to be determined.

Risperidone-associated new-onset diabetes

BACKGROUND Weight gain, and its associated complications such as the development of diabetes, is becoming increasingly recognized as an important potential side effect of the novel antipsychotic drugs. METHODS Two retrospective cases are described in which patients with schizophrenia developed diabetes while taking the antipsychotic medication risperidone. RESULTS Both patients had preexisting risk factors for diabetes and developed insulin resistance in the context of weight gain. Both cases necessitated medical intervention and one patient requires ongoing treatment with insulin. CONCLUSIONS Although the exact mechanism of antipsychotic induced diabetes remains obscure, weight gain appears to be a significant risk factor. Careful monitoring of weight and fasting glucoses is recommended for any patient taking novel antipsychotic medications.

Sexual side effects of novel antipsychotic medications

BACKGROUND The novel antipsychotic medications offer a more favorable extrapyramidal side effect profile than conventional agents. It is uncertain that the novel antipsychotics have a benefit in terms of sexual side effects. METHODS We prospectively administered a survey of sexual functioning to 25 male patients with DSM-IV schizophrenia, taking conventional and novel antipsychotics. Contrasts were made between three treatment groups: clozapine (CLOZ), risperidone (RIS), and a combined haloperidol/fluphenazine (HAL/FLU) group. RESULTS A decrease in overall sexual functioning was reported in all medication groups (40-71%). The majority of subjects taking RIS or HAL/FLU reported a decline in one or more aspects of sexual functioning. Examining specific aspects of sexual functioning revealed that, a decline in sexual interest was significantly less common on CLOZ compared to RIS (0 vs. 64%; chi(2)=6.1, df=1, p=0.01) or HAL/FLU (0 vs. 67%; chi(2)=5.2, df=1, p=0.02), while a decline in the erectile frequency was significantly more common on RIS compared to CLOZ (40 vs. 93%; chi(2)=6.2, df=1, p=0.01) or HAL/FLU (50 vs. 93%; chi(2)=4.8, df=1, p=0.03) (0%). For enjoyment of orgasm and ejaculatory volume, significantly fewer CLOZ compared to RIS subjects reported a decline (20 vs. 86%; chi(2)=7.4, df=1, p=0.01). CONCLUSIONS Sexual side effects are common clinically pertinent adverse effects associated with both novel and conventional antipsychotic medications. They deserve increased attention in clinical work and future research with emerging antipsychotic drugs.

Prevalence of the metabolic syndrome in veterans with schizophrenia.

The metabolic syndrome has become a focus of clinical attention due to its high prevalence in the United States (23%) and impact on cardiovascular risk, yet limited data exist on the prevalence of this syndrome among U.S. veterans with schizophrenia. Methods: A convenience sample of patients diagnosed with schizophrenia or schizoaffective disorder was obtained from inpatient units and outpatient clinics at Veterans Affairs medical centers in San Diego and Los Angeles. Results: In this predominantly male (92.5%) sample of 80 veterans, with mean age of 49.0 years, the age-adjusted prevalence of the metabolic syndrome was 51.2%, more than twice the age-adjusted prevalence in the general U.S. population. The female cohort was small (n = 6), but had a greater mean body mass index and higher prevalence of metabolic syndrome than the male subjects. Conclusions: The metabolic syndrome is highly prevalent in this sample of patients with schizophrenia and represents an enormous source of cardiovascular disease risk. Clinicians who treat patients with schizophrenia should monitor for the parameters that define the metabolic syndrome as part of the ongoing management of patients treated with antipsychotics.

Faith or delusion? At the crossroads of religion and psychosis.

In clinical practice, no clear guidelines exist to distinguish between “normal” religious beliefs and “pathological” religious delusions. Historically, psychiatrists such as Freud have suggested that all religious beliefs are delusional, while the current DSM-IV definition of delusion exempts religious doctrine from pathology altogether. From an individual standpoint, a dimensional approach to delusional thinking (emphasizing conviction, preoccupation, and extension rather than content) may be useful in examining what is and is not pathological. When beliefs are shared by others, the idiosyncratic can become normalized. Therefore, recognition of social dynamics and the possibility of entire delusional subcultures is necessary in the assessment of group beliefs. Religious beliefs and delusions alike can arise from neurologic lesions and anomalous experiences, suggesting that at least some religious beliefs can be pathological. Religious beliefs exist outside of the scientific domain; therefore they can be easily labeled delusional from a rational perspective. However, a religious belief’s dimensional characteristics, its cultural influences, and its impact on functioning may be more important considerations in clinical practice.

The six most essential questions in psychiatric diagnosis: a pluralogue part 1: conceptual and definitional issues in psychiatric diagnosis

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM - whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article will take up the first two questions. With the first question, invited commentators express a range of opinion regarding the nature of psychiatric disorders, loosely divided into a realist position that the diagnostic categories represent real diseases that we can accurately name and know with our perceptual abilities, a middle, nominalist position that psychiatric disorders do exist in the real world but that our diagnostic categories are constructs that may or may not accurately represent the disorders out there, and finally a purely constructivist position that the diagnostic categories are simply constructs with no evidence of psychiatric disorders in the real world. The second question again offers a range of opinion as to how we should define a mental or psychiatric disorder, including the possibility that we should not try to formulate a definition. The general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances.

Understanding the new and evolving profile of adverse drug effects in schizophrenia

This article has reviewed the emerging side-effect profiles of second-generation antipsychotic medications. Although these medications have favorable extrapyramidal side-effect profiles, clinicians must be aware of their propensity to cause weight gain, glucose and lipid abnormalities, and cardiac and sexual side effects. If clinicians are proactive about warning patients about these side effects and appropriately monitoring them, further morbidity and mortality may be prevented in this patient population. Initial choices of medication should be made based on the relative side-effect profiles in light of a particular patients medical status. In the future, new treatments may be developed, with even fewer side effects.

Possible association of QTc interval prolongation with co-administration of quetiapine and lovastatin

BACKGROUND QTc interval prolongation can occur as a result of treatment with both conventional and novel antipsychotic medications and is of clinical concern because of its association with the potentially fatal ventricular arrhythmia, torsade de pointes. METHODS One case is described in which a patient with schizophrenia, who was being treated for dyslipidemia, developed a prolonged QTc interval while taking quetiapine and lovastatin. RESULTS QTc returned to baseline when the lovastatin dose was reduced. CONCLUSIONS QTc prolongation associated with antipsychotic medication occurs in a dose-dependent manner. We therefore hypothesize that the addition of lovastatin caused an increase in plasma quetiapine levels through competitive inhibition of the cytochrome P(450) (CYP) isoenzyme 3A4. Our case highlights the potential for a drug interaction between quetiapine and lovastatin leading to QTc prolongation during the management of dysipidemia in patients with schizophrenia.

The six most essential questions in psychiatric diagnosis: a pluralogue part 3: issues of utility and alternative approaches in psychiatric diagnosis.

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM – whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part 1 of this article took up the first two questions. Part 2 took up the second two questions. Part 3 now deals with Questions 5 & 6. Question 5 confronts the issue of utility, whether the manual design of DSM-III and IV favors clinicians or researchers, and what that means for DSM-5. Our final question, Question 6, takes up a concluding issue, whether the acknowledged problems with the earlier DSMs warrants a significant overhaul of DSM-5 and future manuals. As in Parts 1 & 2 of this article, the general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances.