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PubMedDate not supplied

Psychotropic drug metabolism in the cancer patient: clinical aspects of management of potential drug interactions.

An overview of drug metabolism, with particular focus on the cytochrome p450 system, is provided in this review. To date, there has been a growing body of literature concerning the cytochrome p450 enzyme, drug-drug interactions and the role of psychotropic medications when co-administered with medications prescribed in the medically ill population. The article provides an ability to cross-reference commonly prescribed medications to their known involvement as substrates, inhibitors or inducers of p450 enzymes. This information will permit the clinician working in an oncologic setting to better predict potential interactions based on available in vitro and in vivo data and choose psychotropics analytically when confronted with a situation of polypharmacy. A knowledge of drug interactions will decrease the uncertainty in prescription of multidrug therapies and minimize the likelihood of diminished drug efficacy or toxic reactions.

Cytochrome P-450 Enzyme System↗

PubMed2001

Psychotropics and drug interactions in the elderly patient.

This short paper attempts to provide a framework to aid the old-age psychiatrist in choosing psychotropic drugs in a way that minimizes the risks of adverse drug reactions. It concentrates on the clinical problems most frequently encountered in old-age psychiatric practice. Older people are at risk of adverse drug interactions because of their higher rate of physical morbidity and increased likelihood of receiving polypharmacy, as well as due to age-related change in drug handling. The strongest evidence for relevant interactions in older people relates to changes in renal excretion (particularly relevant for lithium) and cytochrome P450 (relevant for a wide range of psychotropic and other drugs). Awareness of potential interactions is important in ensuring safe prescribing practice for older people with mental health problems.

Aged↗

PubMed1995

Free radicals, anticonvulsants, and the neuronal ceroid-lipofuscinoses.

The relationship between free radicals and scavenger enzymes, and the disorders called the neuronal ceroid-lipofuscinoses, has long been an argumentative one. Recent evidence would seem to support the fact that such a relationship might exist but that it is indirect. The relationship does not seem due to an inborn error of free radical scavenger enzyme metabolism. Anticonvulsants play a role, as they influence free radical generating systems. At this juncture, no one has studied the relationship of anticonvulsant therapy, neuronal ceroid-lipofuscinosis, and the free radical-scavenging enzyme system, and their interplay. We have studied a large number of patients with epilepsy who are on either monotherapeutic or polytherapeutic regimens of most of the common anticonvulsants. We have found excessive free radical production in many of these patients, ranging from minor effects in the simpler anticonvulsants when used monotherapeutically, to more complex changes in polytherapeutic combinations. Likewise, we have found subtle and inconsistent findings in the free radical-scavenging enzyme system in a variety of examples of neuronal ceroid-lipofuscinosis. When refractory seizure disorders stimulate the vigorous use of polytherapy with a variety of free radical-facilitating anticonvulsants, free radical production becomes deleterious. Likewise, in certain types of neuronal ceroid-lipofuscinosis, polypharmacy with anticonvulsants, by enhancing the production of free radicals or suppressing scavenging enzymes, tends to be deleterious and induces a worsening in the disease process.

Adolescent↗

PubMed2006

CYP2D6 genotype and venlafaxine-XR concentrations in depressed elderly.

INTRODUCTION: The elderly are at increased risk for medication-related adverse events. Recent reports indicate that venlafaxine may put the elderly at increased risk of cardio- and cerebrovascular adverse events. We investigated the relationship between the CYP2D6 polymorphism and steady-state plasma concentration of venlafaxine (VEN) and its primary metabolite o-desmethylvenlafaxine (ODV) in elderly participants receiving venlafaxine-XR for major depression in order to explore the contribution of pharmacogenetics to medication tolerability. METHODS: Forty-six elderly participants received venlafaxine-XR for the treatment of major depression. CYP2D6 genotype and steady-state plasma levels of VEN and ODV were determined. RESULTS: Sixty-five percent of participants were homozygous of the wild type (WT) allele, whereas 35% carried one or more variant alleles associated with intermediate and poor 2D6 metabolizer status. VEN concentration per unit dose was significantly higher and ODV concentration per unit dose was significantly lower in participants who carried one or more variant alleles compared to participants who were homozygous for the WT allele. The VEN and ODV concentrations per unit dose were also correlated with creatinine clearance. CYP2D6 genotype was not associated with medication associated side-effects. CONCLUSIONS: Plasma dose-corrected concentrations of VEN and ODV correlated with genetically determined CYP2D6 enzymatic activity in depressed elders treated with venlafaxine-XR. This relationship was not masked by the effects of age-related illness or polypharmacy. Future clinical application of pharmacogenetics to examine 2D6-dependent medications may help reduce the incidence of medication adverse events particularly in those elders at higher risk for medication adverse events due to impaired renal or cardiac function.

Aged↗

PubMed2002

Psychotropics among the home-dwelling elderly--increasing trends.

OBJECTIVE: To assess the level of and changes in the use of psychotropics among the home-dwelling elderly in the 1990s. METHODS: A descriptive analysis based on data from two cross-sectional interview and health examination surveys of elderly persons aged 64 years or over conducted in Lieto, a typical semi-rural Finnish municipality, in 1990-91 and 1998-99. National prescription data were utilized to compare the use of psychotropics in the late 1990s by all Finnish home-dwelling elderly and the elderly in Lieto. In Lieto drug information was obtained from 1131 persons in 1990-91 and from 1197 in 1998-99, and the mean age of the informants was 73 years in both surveys. The brand names of the prescription drugs (both irregular and regular medication) taken by each interviewee during seven days prior to the interview were recorded and categorized by the Anatomical Therapeutic Chemical (ATC) classification system. RESULTS: Every fourth person was taking at least one psychotropic drug in both surveys. Most users were on regular psychotropic medication. The use of hypnotics and antidepressants increased most during the study period. Polypharmacy and the use of psychotropics were most prevalent among those aged 85 years or over, with women predominating. Concomitant use of two or more psychotropics increased statistically significantly from 7% to 10% between the surveys. The young elderly, aged 64-71 years, used cyclic antidepressants equally commonly in both surveys. None of the young elderly used new atypical antipsychotics in 1998-99. CONCLUSIONS: Psychotropics tend to be overprescribed and overused among the elderly, a group at the highest risk of adverse drug reactions. The tendency of prescribing for the elderly is not going in a better direction. New-generation psychotropics were not used. The need for long-standing use of psychotropics should be assessed regularly.

Aged↗

PubMed2003

Death rates from ecstasy (MDMA, MDA) and polydrug use in England and Wales 1996-2002.

The present study reports on all deaths related to taking ecstasy (alone, or in a polydrug combination) occurring in England and Wales in the time frame August 1996-April 2002. Data presented here are based on all information recorded in the National Programme on Substance Abuse Deaths (np-SAD) database. The np-SAD regularly receives all information on drug related deaths in addicts and non addicts from coroners. A total of 202 ecstasy-related fatalities occurred in the chosen time-frame, showing a steady increase in the number of deaths each year. The ratio male:female was 4:1 and 3 of 4 victims were younger than 29. In 17% of cases ecstasy was the sole drug implicated in death and in the remaining cases a number of other drugs (mostly alcohol, cocaine, amphetamines and opiates) have been found. According to toxicology results, MDMA accounted for 86% of cases and MDA for 13% of cases; single deaths were associated with MDEA and PMA. This is the largest sample of ecstasy related deaths so far; possible explanations are given for the observed steady increase in ecstasy-related deaths and a tentative 'rationale' for this polypharmacy combination is then proposed.

3,4-Methylenedioxyamphetamine↗

PubMed2004

Dosage finding and outcome in the treatment of schizophrenic inpatients with amisulpride. Results of a drug utilization observation study.

OBJECTIVES: Amisulpride is an unique neuroleptic drug insofar as it has a dual pharmacodynamic effect. At low doses it blocks selectively presynaptic autoreceptors, and at high doses it blocks postsynaptic D(2)/D(3) receptors. This allows the dosage to be adjusted and the treatment tailored to various clinical situations. It is unknown whether this pharmacological property has any bearing for routine treatment. The questions are: which dosages of amisulpride are chosen by physicians in the treatment of schizophrenic inpatients and does this dosage handling deviate from prescription guidelines?; which factors can explain dosage selection, and what is the treatment outcome with different dosages? The study pertains to drug management and dosage finding as principal factors in explaining positive and negative medication results. METHODS: In a drug utilization observation study the prescribing of amisulpride for 811 schizophrenic inpatients from 240 psychiatric hospitals was monitored for 8 weeks. Standardized assessment included dosage, the positive and negative symptom scale (PANSS), the clinical global impression rating (CGI), the patients' subjective reaction to amisulpride, psychosocial functioning, EPS and other adverse events. The mean observation period was 49 days. RESULTS: The mean initial daily dose of amisulpride was 361 mg/day. The mean daily dose at day 56 was on average 550 (SD 266) mg/d, ranging from 100 mg to 1600 mg. 17.9% of patients received a maximum dose up to 399 mg/d, 48.1% between 400 and 799 mg/d, and 25.5% 800 mg/d and higher. Higher doses were preferably prescribed for males, patients with involuntary admission, patients with paranoid schizophrenia with acute exacerbation, high CGI and high PANSS-positive scores. Patients with higher doses of amisulpride at the same time received higher rates of additional other neuroleptic drugs. Higher doses yield better results in very severe cases. CONCLUSIONS: Prescribed dosages were in the lower range of what is recommended for acute cases. Dosage was significantly influenced by the severity of the illness. Polypharmacy was the rule rather than the exception. Efficacy rates under conditions of routine care were similar to the results from controlled clinical trials, which speaks for their generalizability. Very severe cases profit from higher doses.

Adult↗

PubMed2007

Clinical correlates of clozapine prescription for schizophrenia in China.

AIMS: Few studies have investigated the prescription patterns of clozapine in outpatients with schizophrenia in China. It is an important issue due to clozapine's high efficacy and potentially fatal side effect profile. This study examined the use of clozapine and its correlates in China. METHODS: Three hundred ninety-eight clinically stable outpatients with schizophrenia were randomly selected and interviewed in Hong Kong (HK) and Beijing (BJ). Assessment instruments included the Structured Clinical Interview for DSM-IV, Brief Psychiatric Rating Scale, Simpson and Angus Scale of Extrapyramidal Symptoms, Barnes Akathisia Rating Scale and the Hong Kong and Mainland China World Health Organization Quality of Life Schedule-Brief version. Assessments were performed by the same investigator in both sites. RESULTS: Clozapine was prescribed to 15.6% of (n = 62) patients. There was a wide inter-site variation between HK and BJ. Use of clozapine was associated with age, age at onset, extrapyramidal side effects (EPS), having health insurance, use of depot and typical antipsychotic and anticholinergic drugs and benzodiazepines as well as history of suicidal attempts. On multiple logistic regression analysis, the number of hospitalizations, site (HK vs. BJ), use of typical antipsychotics, polypharmacy and co-prescription with anticholinergics were significantly associated with the prescription of clozapine. No significant differences were found between the clozapine and non-clozapine groups with regard to any of the quality of life domains. CONCLUSION: A combination of economical and clinical factors, health policies and the characteristics of the treatment settings plays important roles in determining clozapine use. Clozapine appears to have little significant influence on quality of life in clinical stable Chinese patients with schizophrenia.

Adult↗

PubMedDate not supplied

Developing a patient self-medication program for the rehabilitation setting.

Self-medication, the ability of the patient to administer his or her own medication, can be useful in the rehabilitation setting in reducing the incidence of polypharmacy, medication abuse, and inappropriate medication usage. However, a patient self-medication program also introduces a variety of issues, such as defining each team member's responsibilities and outlining the steps of the program. These issues may impede the development and implementation of the program. A review of the rehabilitation literature yields little information about program development in the rehabilitation setting or about dealing with such issues. The purpose of this article is to describe the need for a self-medication program in the rehabilitation setting, the development of one such program, and ways to overcome some of the problems that cause such programs to falter.

Humans↗

PubMed2005

HPLC-DAD determination of plasma levels of the antipsychotic risperidone and its main metabolite for toxicological purposes.

A new, rapid analytical method, based on liquid chromatography with diode array detection, has been developed and applied to the determination of risperidone and its main active metabolite 9-hydroxyrisperidone in human plasma. The chromatographic separation was obtained on a C8 (150 x 4.6 mm, 5 microm) column, using a mobile phase composed of acetonitrile (27%) and a pH 3.0 phosphate buffer (73%). A sample clean-up procedure was carried out by using C8 cartridges and eluting the analytes with methanol. The extraction yield was highly satisfactory for both analytes, with average absolute recovery values of about 95%. The experimental conditions permitted the quantitative determination of risperidone and 9-hydroxyrisperidone with high precision (RSD < 3.6%) and satisfactory sensitivity (LOQ = 4 ng mL(-1)). The method was applied to plasma samples from a patient who had tried to poison himself with 150 mg of risperidone, and was undergoing polypharmacy.

Antipsychotic Agents↗

PubMed2003

Psychosis in Parkinson's disease.

Psychosis is a disabling nonmotor complication of Parkinson's disease (PD). Visual hallucinations are the most common clinical manifestation and have been observed in up to 40% of patients with advanced disease in hospital-based series. Age, cognitive dysfunction, depression, as well as severity and duration of disease have all been identified as risk factors in multiple studies. All major antiparkinsonian drugs can induce psychosis in at-risk patients. Early drug-induced psychosis has been observed in up to 16% of patients treated with dopamine agonists and has been associated with increased risk for the development of dementia later on. Management of psychosis in PD is complex and includes control of potential triggers and reductions of polypharmacy as well as the addition of atypical antipsychotics. Cholinesterase inhibitors may prove an additional option in psychotic PD patients with dementia.

Antiparkinson Agents↗

PubMed2004

Painful peripheral neuropathy and its nonsurgical treatment.

Treatment of neuropathic pain is the primary focus of management for many patients with painful peripheral neuropathy. Antidepressants and anticonvulsants are the two pharmacological classes most widely studied and represent first-line agents in the management of neuropathic pain. The number of pharmacological agents that have demonstrated effectiveness for neuropathic pain continues to expand. In the current review, we summarize data from randomized, controlled pharmacological trials in painful peripheral neuropathies. Although neuropathic pain management remains challenging because the response to therapy varies considerably between patients, and pain relief is rarely complete, a majority of patients can benefit from monotherapy using a well-chosen agent or polypharmacy that combines medications with different mechanisms of action.

Analgesics↗

PubMed2006

Mortality in schizophrenia.

PURPOSE: The purpose of this article is to describe the current status of knowledge on excess mortality in schizophrenia and its causative factors, and to expand upon previous work evaluating approaches that may reduce mortality rates. METHODS: Literature available since 1995 was identified in a computerized search of the bibliographical databases Medline and Embase, using the topics 'mortality' and 'schizophrenia', and in a cross-reference search for articles that were particularly relevant. RESULTS: Schizophrenia is associated with mortality rates that are two to three times higher than those expected or observed in the general population. This excess of mortality is accounted for by a combination of an increased risk of suicide, in particular in young male patients soon after diagnosis, and more importantly, a higher number of natural deaths. In order to diminish the level of suicide among people with schizophrenia, the majority of research has focused on the identification of risk factors that predispose patients to attempt or commit suicide, while unhealthy styles, polypharmacy and inadequate healthcare have been shown to contribute to the high natural mortality. The link between the use of antipychotics and mortality has not been yet clarified. CONCLUSION: Dramatically increased mortality of schizophrenia patients is well established. It is time to move beyond this topic, and work towards interventions that aim at reducing the mortality risk in such patients.

Antipsychotic Agents↗

PubMed1995

Glutamate/dopamine D1/D2 balance in the basal ganglia and its relevance to Parkinson's disease.

The recent availability of selective ligands for NMDA and AMPA receptors has enabled neuroscientists to test the hypothesis that Parkinson's disease is a glutamate hyperactivity disorder and hence treatable with glutamate antagonists. This review takes a critical look at the motor characteristics of this new class of drugs in rodent and primate models of parkinsonism and assesses the clinical potential and pitfalls of this radical new approach. Monotherapy of Parkinson's disease with glutamate antagonists appears impractical at the present time, due to their low efficacy and unacceptable side effects, but polypharmacy with L-DOPA and a glutamate antagonist as adjuvant is a more realistic prospect. This review will focus on the ways in which glutamate receptor blockade facilitates motor recovery with L-DOPA and will examine whether the basis for this beneficial effect can be traced to a specific interaction with dopamine at D1 or D2 receptors, and therefore to discrete motor pathways within the basal ganglia.

Animals↗

PubMed1997

Treatment of agitation in dementia.

Agitation occurs commonly in patients with dementia. Before symptomatic pharmacotherapy is undertaken, it is imperative to perform a sequence of evaluations and interventions to establish whether simpler and safer, nonpharmacologic approaches will be beneficial. When psychotropic medications are used they should be used judiciously, in the lowest effective doses and for the shortest period of time necessary. Ineffective medications should be stopped, and even effective medications should be empirically tapered in most patients to learn whether treatment is still necessary. Antipsychotics probably show the greatest benefit for agitation associated with psychotic features; they have less demonstrated efficacy for agitation not associated with psychotic features. The side effects of typical agents are legion; data are pending regarding atypical agents. The available evidence regarding nonneuroleptic medications ranges from case reports to well-designed, double-blind, placebo-controlled, randomized, parallel group studies. Literature exists describing the use of anticonvulsants, anxiolytics, serotonergic antidepressants, and other agents to manage agitation. Carbamazepine and divalproex sodium (valproate) have demonstrated efficacy in uncontrolled studies, whereas the use of carbamazepine has produced negative results in one small controlled study and positive results in two larger controlled studies. Buspirone has shown benefit in some open trials. Encouraging early findings have been reported for trazodone, including from one controlled trial. Varying results have been obtained using selective serotonin reuptake inhibitors, but with consistently encouraging anecdotes. In the aggregate, the evidence suggests but does not prove that alternatives to traditional antipsychotics exist. Again, none of these agents has yet been approved for this purpose by the FDA. As more studies become available we will have a better idea about which classes of agents are most efficacious. It is likely that there may be a role for "rational" polypharmacy in the management of this distressing complication of dementia. However, no studies that we know of address combination therapy, so the clinician must contemplate this option on a case-by-case basis. Clinical trials data are pending from studies with divalproex sodium, carbamazepine, haloperidol versus trazodone versus placebo, risperidone, olanzapine, quetiapine, donepezil, xanomeline, tacrine, buspirone, and sertraline, at the very least. These data will undoubtedly have a major impact on how we care for our patients and lead to revisions of current practice guidelines.

Aged↗

PubMed1990

Extrapyramidal symptoms in neuroleptic recipients.

Adverse drug reactions (ADRs) in psychiatric therapy were continuously assessed in the AMUP study (AMUP = Arzneimittelüberwachung in der Psychiatrie (drug surveillance in psychiatry] conducted at two psychiatric university departments in the F.R.G. The Intensive Drug Monitoring (IDM) method was used to monitor 1107 patients, 754 of whom received neuroleptics (NLs). As is the rule in clinical psychiatric practice, polypharmacy was frequent, with combinations of two neuroleptics and combinations of a neuroleptic and an antiparkinson drug ranking first and second, respectively. Extrapyramidal motor symptoms (EPMS) were observed in 35% of the NL patients. In most cases they required a change in medication, usually addition of an antiparkinson drug. In about one quarter of all EPMS cases, withdrawal of the imputed NL was necessary. Parkinsonism was the most frequent single symptom, followed by acute dystonia and akathisia. Differences in EPMS rates between the two most frequently used neuroleptics, haloperidol, a high-potency butyrophenone, and perazine, a medium-potency phenothiazine, were distinct. EPMS were observed with haloperidol in 56% and attributed to haloperidol alone in 92% of these cases. With perazine, an EMPS occurred at a rate of only 14%, and in 37% of the cases EMPS were attributable to perazine in combination with other NLs. Age, sex, diagnosis and dosage of administered NLs were closely interrelated. For instance, NL patients over 60 years of age were almost exclusively female, the majority of them being endogenous depressives, whereas in younger patients the diagnosis of schizophrenia prevailed. Therefore, analysis of potential risk factors for development of EPMS must simultaneously include diagnosis, sex and age as well as concomitant physical disease, duration and dosage of all drugs administered before development of EPMS. However, the small case numbers in some subgroups, as we found them in this study based on everyday clinical practice, will probably be a limiting factor in such multivariate analyses.

Acute Disease↗

PubMed2003

New developments in the pharmacotherapy of schizophrenia.

This review summarizes current key research strategies and the most prominently pursued new potential treatments for schizophrenia. First, new routes of administration for second generation antipsychotics are presented. These include rapidly dissolving tablets, drops and sirups as well as new intramuscular formulations. Newly available short acting and long acting (depot) antipsychotics complement oral antipsychotics so that the full spectrum of routes of administration is now available for second generation antipsychotics. Next to antipsychotic polypharmacy, in which two or more antipsychotics are combined, pharmacological add-on treatments, mainly with benzodiazepines, antidepressants and mood stabilizers enjoy increasing popularity. Most of this practice is driven by personal preferences, clinical experience and marketing rather than evidence based medicine. New pharmacological mechanisms currently utilized in advanced states of development include partial dopamine D2-receptor agonism, supplementation with glutamatergic agents, estrogen and omega-3-fatty acids. While the concept of partial D1-agonism has already led to the successful launch of a new antipsychotic, aripiprazole, the other attempts to improve therapeutic response in schizophrenia patients have so far provided equivocal results. It is argued that they may be helpful for certain subgroups or specific symptoms of schizophrenia patients. In conclusion, many exciting new pharmacological leads are currently pursued and this will very likely augment the options for treating patients with schizophrenia.

Antipsychotic Agents↗

PubMed1990

Risk factors for adverse drug reactions--epidemiological approaches.

Age by itself is not an important risk factor for ADRs. Age-related changes are the consequence of a number of individual factors, for example morbidity associated with polypharmacy, decline in renal or liver function in the elderly, hypoalbuminaemia, reduced body weight, etc. The relationship between gastrointestinal bleeding and non-steroidal anti-inflammatory drugs can be assessed globally in large cohort studies with access to computerized data, but complete accuracy requires access to the original patient records. The increase in the risk of GI bleeding in users of NSAIDs and aspirin was 50% above that in non-users. About a quarter of ADRs in hospitalized patients seem not to arise from purely pharmacological mechanisms. They are mainly due to allergic, anaphylactoid, or idiosyncratic reactions and to intolerance. In such non-pharmacological reactions, the time of exposure, reaction time, and even dosage may be important factors in identification of the causal drug. The use of benzodiazepines can be optimized by taking into account potency, time of action and the different syndromes encountered after withdrawal. Following long-term use problems of relapse and rebound are being increasingly recognized, in addition to organic withdrawal symptoms. In psychiatric patients extrapyramidal disorders due to neuroleptics are common. The rates of these ADRs differ markedly between various drugs, even after dosages and co-medications are taken into account. Epidemiological screening for potentially carcinogenic drugs can only be done in large cohorts of patients with pre-recorded full information sets as may be found in an HMO (Health Maintenance Organization). The findings of several such studies have been published in specialist cancer journals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗