Showing papers on "Psychotropic drug published in 2006"

Endocrine and metabolic adverse effects of psychotropic medications in children and adolescents

Abstract: Objective: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. Method: Selective review of endocrine and metabolic effects of psychotropic medications in pediatric populations, with a focus on monitoring and management strategies. Results: Because youth are still developing at the time of psychotropic drug exposure, most reference values need to be adjusted for gender and age. As in adults, youngsters receiving lithium require monitoring for thyroid dysfunction. Psychostimulants appear to cause mild reversible growth retardation in some patients, most likely because of decreased weight or slowing of expected weight gain; some patients may experience clinically significant reductions in adult height. Although still controversial, valproate use has been associated with an increased risk for polycystic ovary syndrome, in addition to causing weight gain. Although more data are required, children and adolescents appear to be at higher risk than adults for antipsychotic-induced hyperprolactinemia, weight gain, and possibly, associated metabolic abnormalities, which is of particular concern. Conclusions: Clinicians and caregivers need to be aware of potential endocrine and metabolic adverse effects of psychiatric medications. A careful selection of patients, choice of agents with potentially lesser risk for these adverse events, healthy lifestyle counseling, as well as close health monitoring are warranted to maximize effectiveness and safety.

Do antidepressants cure or create abnormal brain states

Abstract: The term antidepressant refers to a drug that helps to rectify specific biological abnormalities that give rise to the symptoms of depression. This exemplifies what we have called the “disease-centred” model of psychotropic drug action [ 1]. Modelled on paradigmatic situations in general medicine—such as the use of insulin in diabetes, antibiotics in infectious disease, chemotherapy in cancer—the disease-centred model suggests that antidepressants help restore normal functioning by acting on the neuropathology of depression or of depressive symptoms. In contrast, we propose in this Essay that an alternative “drug-centred” model can better explain observed drug effects in psychiatric conditions. This drug-centred model suggests that instead of relieving a hypothetical biochemical abnormality, drugs themselves cause abnormal states, which may coincidentally relieve psychiatric symptoms ( Table 1). Alcohol's disinhibiting effects may relieve symptoms of social phobia, but that does not imply that alcohol corrects a chemical imbalance underlying social phobia. Sedation may lessen high arousal, present in many acute psychiatric situations. Drugs that induce indifference, such as neuroleptics or opiates, may help reduce the distress of acute psychotic symptoms. Low-dose stimulants may help improve attention and concentration in the short term. Table 1 Main Assumptions of Two Models of Psychotropic Drug Action The disease-centred model in psychiatry leads researchers to infer antidepressant effects from patients' scores on symptom rating scales presumed to assess the manifestations of the disease. The drug-centred model, on the other hand, suggests that physiological and subjective effects of drugs should be examined in their own right. These effects include various forms of sedation, stimulation, and a plethora of biopsychological states. Depending on individual inclination and context (including a person's emotional state upon drug ingestion), intoxication with some drugs produces euphoria or mood elevation. Because tolerance develops, however, euphoriant effects do not persist with long-term use. If antidepressants or any other psychotropic drugs could be shown to have mood-elevating effects that were long-term and not diminished by being in a depressed emotional state, this would distinguish them from psychotropic drugs that cause euphoria and might prove uniquely useful in depressed patients (see Sidebar).

Increased medial thalamic creatine-phosphocreatine found by proton magnetic resonance spectroscopy in children with obsessive-compulsive disorder versus major depression and healthy controls.

Abstract: Altered brain creatine-phosphocreatine levels might reflect changes in brain energy use and have been implicated in the pathogenesis of obsessive-compulsive disorder and major depressive disorder. We used proton magnetic resonance spectroscopy to measure absolute concentrations of creatine-phosphocreatine in the right and left medial thalami in 18 pediatric patients with major depressive disorder 9 to 17 years of age, 18 case-matched healthy controls, and 27 patients with obsessive-compulsive disorder 7 to 16 years old. The two patient groups were psychotropic drug naive and were not comorbid for the diagnosis of the comparison group. We found significantly increased left and right medial thalamic creatine-phosphocreatine concentrations in patients with obsessive-compulsive disorder compared with both healthy controls and patients with major depression. Creatine-phosphocreatine concentrations did not differ significantly between patients with major depression and healthy controls. Our data suggest that increased medial thalamic creatine-phosphocreatine concentrations in patients with untreated obsessive-compulsive disorder reflect altered energy use in the medial thalamus and might differentiate patients with obsessive-compulsive disorder from healthy controls and patients with major depression. Although these results must be considered preliminary, further study of the diagnostic specificity of creatine-phosphocreatine in obsessive-compulsive disorder is indicated.

Factors associated with psychotropic drug usage among nursing home residents with dementia.

Abstract: Background: Although federal regulations hold nursing homes responsible for monitoring psychotropic drug (PD) usage, there is a high prevalence of PD usage and significant variation in use across nursing homes. Objectives: The aims of study were to (a) describe current PD usage in nursing homes and (b) examine resident and nursing home factors associated with PD usage in nursing home residents with dementia. Methods: A multivariate, multisite, cross-sectional descriptive study was used on data from 107 dementia patients residing in nine randomly selected nursing homes in southeastern Michigan. The PD usage of interest included antipsychotics, antidepressants, anxiolytics or sedatives, and mood stabilizers. Regression analysis tested resident factors, including cognitive ability, functional ability, presence of depressive symptoms, and demographic characteristics, and three facility factors (nursing home size, type of ownership, and level of registered nurse [RN] staffing) in comparison with PD usage. Results: In this study. 67.3% of the participants received at least one PD. The most frequently prescribed PDs were antidepressants (41.1%) and antipsychotics (37.4%). Newly developed antipsychotics such as risperidone were given more frequently to residents than were conventional drugs such as haloperidol. Regression analysis suggests that the presence of depressive symptoms (odds ratio [OR] = 3.5, p <.01) and low levels of RN staffing (OR = 1.0, p <.01) were associated with the use of PD. Discussion: Psychotropic drugs are prescribed frequently for nursing home residents, although such usage is variable. Behavioral symptoms were not an independent predictive factor for PD use. Rather, combined resident and facility characteristics best predicted the use of PDs in nursing home residents. The evaluation of nursing home systems for these characteristics as predictive factors for PD usage in nursing home patients with dementia is suggested by the results. Likewise, attention to new drugs such as selective serotonin reuptake inhibitors and their appropriate use is recommended.

Psychotropic medication utilization in a child and adolescent mental health service.

Abstract: Objectives: This study aimed to identify rates and correlates of psychotropic drug utilization in children and adolescents in inpatient and outpatient settings. Methods: A retrospective chart review examined 122 inpatient and 126 outpatient charts from a metropolitan child and youth mental health service in Brisbane, Australia. Results: Inpatients received more psychotropic medication than outpatients (71% vs. 25%; p 1 concurrent drug), with up to four drugs used at one time. Rates of polypharmacy were highest among patients receiving antipsychotics. Conclusions: Use of psychotropic medication is frequent in this population. Future research should initially focus on inpatients and intensive treatment settings and examine both safety and efficacy of interventions for depression in young people, atypical antipsychotics for behavioral disturbances, and polypharmacy.

Sexual dysfunction and psychotropic medications.

Abstract: Psychotropic drugs are often associated with sexual dysfunction. The frequency of antidepressant-associated sexual dysfunction is greatly underestimated in clinical trials that rely on patient self-report of these adverse events. Direct inquiry reveals that delayed orgasm/ejaculation occurs in >50% and anorgasmia in at least one third of patients given selective serotonin reuptake inhibitors. Antidepressant-induced sexual dysfunction can be successfully managed. A different antidepressant without significant sexual effects, such as bupropion or mirtazapine, can often be substituted. Other strategies involve drug holidays or adjunctive therapy with drugs such as sildenafil. Dopamine antagonist antipsychotic drugs are most commonly associated with decreased libido. The newer atypical antipsychotics, with less effect on dopamine, are less commonly associated with sexual dysfunction. Sexual dysfunction is commonly reported with seizure disorders, and many anticonvulsant drugs affect levels of sex hormones. Because sexual dysfunction can be related to many factors, care must be taken to establish the patient's baseline sexual functioning before the initiation of psychotropic drug therapy and to rule out other etiologies before drugs are implicated as causative.

Current use of psychotropic medication in nursing homes

Abstract: Objective To examine the current pattern of use of psychotropic medication in Sydney nursing homes and compare this with the pattern noted 5 and 10 years earlier. Method Data were recorded from medication cards concerning psychotropic medications prescribed for the 3093 residents in the 51 nursing homes in the Central Sydney Health Area. Documented diagnoses and demographic details were noted from their clinical files. Results In late 2003, 47.2% of residents were taking one or more psychotropic drug regularly and another 3.5% had been given "as required" (prn) doses at least once in the preceding 4 weeks. Fewer residents were taking hypnotics (11.3%) and anxiolytics (4.1%) regularly, when compared to 1998, but more were taking antidepressants (20.5%). Selective serotonin reuptake inhibitors were prescribed to 11.4%, venlafaxine to 2.6%, mirtazapine 1.6% and tricyclics to 3.6%. Although the proportion taking antipsychotics had not fallen since 1998, there were over twice as many residents (16.4%) taking atypical neuroleptic medication in 2003 as there were taking conventional neuroleptics (8.1%). Most of them did not have schizophrenia. Conclusions There have been further reductions in the use of hypnotics and anxiolytics in Sydney nursing homes, with increased prescription of antidepressants and a striking change towards use of atypical rather than conventional neuroleptic medication.

Pharmaco-EEG in Psychiatry:

Abstract: In spite of its origins deeply rooted in the discipline, pharmaco-EEG applications in psychiatry remain limited to its achievements in the field of psychotropic drugs classification and, in few instances, discovery. In the present paper two attempts to transfer pharmaco-EEG methods to psychiatric clinical routine will be described: 1) monitoring of psychotropic drug toxicity at the central nervous system level, and 2) prediction of clinical response to treatment with psychotropic drugs. Both applications have been the object of several investigations providing promising and sometimes consistent findings which, however, had no impact on clinical practice. For the first topic, the review is limited to antipsychotics, lithium and recreational drugs, as for other psychotropic drugs mostly case studies are available, while for the response prediction it will include antipsychotics, antidepressants, anxiolytics, psychostimulants and nootropics. In spite of several methodological limitations, pharmaco-EEG studies dealing with monitoring of antipsychotic- and lithium-induced EEG abnormalities went close to, but never became, a clinical routine. EEG studies of recreational drugs are flawed by several limitations, and failed, so far, to identify reliable indices of CNS toxicity to be used in clinical settings. Several QEEG studies on early predictors of treatment response to first generation antipsychotics have produced consistent findings, but had no clinical impact. For other psychotropic drug classes few and inconsistent reports have appeared. Pharmaco-EEG had the potential for important clinical applications, but so far none of them entered clinical routine. The ability to upgrade theories and methods and promote large scale studies represent the future challenge.

The prescription of psychotropic drugs in psychiatric residential facilities: a national survey in Italy.

Abstract: Objective: This paper reports the prescriptions of psychotropic drugs made to 2962 patients living in 265 residential facilities (RFs) in Italy. Method: Structured interviews were administered to RF managers and staff to obtain data on patients’ sociodemographic and clinical characteristics; information about current drug prescriptions were obtained from clinical records. Results: Polypharmacy was common: on average, each treated patient was taking 2.7 drugs (±1.1). The association of one atypical antipsychotic with one benzodiazepine represented the most common prescription profile. The variable most consistently associated with a higher likelihood of receiving polypharmacy was a history of admission to an acute general hospital psychiatric ward in the previous 12 months. Many prescriptions were loosely related to specific diagnoses. Conclusion: Psychotropic drug prescription patterns for severe patients living in RFs are characterized by substantial rates of polypharmacy. Specific guidelines may be helpful for long-stay patients living in RFs, who exhibit complex care needs.

On cannabis, chloral hydrate, and career cycles of psychotropic drugs in medicine.

Abstract: This article compares the careers of two psychotropic drugs in Western psychiatry, with a focus on the nineteenth century: Cannabis indica and chloral hydrate. They were used by doctors for similar indications, such as mania, delirium tremens, and what we would now call drug dependence. The two show similar career paths consisting of three phases: initial enthusiasm and therapeutic optimism; subsequent negative appraisal; and finally, limited use. These cycles, which we term "Seige cycles," are generally typical of the careers of psychotropic drugs in modern medicine. However, differences in the careers of both drugs are also established. The phases of chloral show relatively higher peaks and lower valleys than those of cannabis. Chloral is the first typically "modern" psychotropic drug; a synthetic, it was introduced in 1869 at a time of growing asylum populations, pharmaceutical interests, and high cultural expectations of scientific medicine. Cannabis indica, introduced in the 1840s, is typically a "premodern" drug steeped in the climate of cultural Romanticism. We conclude that the analytical concept of the Seige cycle is a useful tool for future research into drug careers in medicine.

Social Workers' Attitudes about Psychotropic Drug Treatment with Youths

Abstract: Given the precipitous rise in psychotropic drug use with youths in recent years (for example, Rushton & Whitmire, 2001; Zito et al., 2003), nearly every social worker practicing with youths has worked with a medicated child or adolescent. Despite the controversies and concerns this trend has generated (see, for example, Ingersoll, Bauer, & Burns, 2004; Moses & Kirk, 2005), we know very little about social workers' attitudes toward this trend. This is unfortunate because social workers provide the largest proportion of mental health services in the United States (Gibelman & Schervish, 1997; Knowlton, 1995), and their attitudes are likely to affect how they broker clients' access to drug treatment and the quality of supportive services that accompany drug treatment (for example, education; monitoring of side effects, adherence, and effectiveness; and collaboration with physicians). Moreover, parents often turn to social workers to ask about medication because social workers often serve as intermediaries among families, schools, and physicians in regard to referrals for medication evaluation and follow-up (Bentley & Walsh, 2001; Taylor, 2003). Social workers' attitudes about drug treatment likely affect their behavior and communication style with clients (Bentley, Farmer, & Phillips, 1991; Taylor, 2003). Johnson and colleagues (1998) found that social workers expressing stronger beliefs that medication is helpful in treating emotionally disturbed youths were also more likely to have favorable attitudes toward collaborative work with other professionals (for example, to refer youths to other specialists) and to work more closely with families (for example, to share information with parents and to avoid attributing blame). Social workers' attitudes toward medication treatment are likely to affect medication referrals. Bradley (2003) noted that social workers' "beliefs and theoretical framework impact why, when, and how this decision [to refer for medication consultation] is made" (p. 36). Moreover, social workers' attitudes are likely to affect clients' receptivity, satisfaction, and response to this form of treatment. A recent survey of social workers' roles in clients' psychiatric medication reported that when asked about their most important personal contribution to a successful outcome with psychiatrically medicated clients, 16 percent of respondents indicated that it was holding positive attitudes and beliefs that support medication (Bentley, Walsh, & Farmer, 2004).These social workers thought that communicating hope and sharing professional experiences of other clients' positive outcomes contributed to positive outcomes. There have been no empirical studies, however, of whether there is a direct relationship between social workers' attitudes toward drug treatment and treatment outcomes. Social Workers" Views of Drug Treatment Much of the earlier social work literature from the 1970s and 1980s depicts the profession's view of psychotropic medication treatment as suspicious and negative (for example, Berg & Wallace, 1987; Davidson & Jamison, 1983; Matorin & De Chillo, 1984).This literature, focused on adult clients, suggests that social workers are resistant to the medical model, a perspective that defines clients' problems using medical-psychopathological terms that are apolitical, decontextualized, and deficit oriented and that steers treatment toward "fixing" the individual. This literature tends to focus on the negative physical or psychosocial consequences of biological interventions and about possible drug misuse involved in inadequate screening, overmedication, and infringement on patients' rights. More recent literature, however, has suggested that many social workers subscribe, at least to some extent, to the medical model and support as well as facilitate the use of drug treatment for adults with mental illness. Several studies of social workers' attitudes toward psychopharmacologic treatment suggest that they are more positive about drug treatment than other mental health professionals (Bentley et al. …

Chromatin remodeling: a novel mechanism of psychotropic drug action.

Abstract: Regulation of gene expression is known to contribute to the long-term adaptations underlying the effects of psychotropic drugs, including the actions of antidepressants and drugs of abuse in behavioral models. However, the precise molecular events that are required for modification of chromatin and that underlie gene repression or activation have not been elucidated. Recent reports, including the article by Cassel et al. (p. 487) in this issue of Molecular Pharmacology, address this question and demonstrate that psychotropic drugs modify specific methyl-CpG-binding proteins that control histone acetylation and gene expression.

Psychotropic drug prescription in a psychiatric university hospital in Germany.

Abstract: A retrospective survey on drug prescription over a 5-year period (1998 to 2003) in 1540 inpatients in a psychiatric university hospital in Germany was carried out. The aim was to establish a basis for a monitoring of prescription habits and for pharmacoeconomic considerations. It was established that there was only a slight increase in polyvalent drug use between 1998 and 2003. The results are presented in more detail in relation to the diagnosis of organic mental disorders, drug abuse disorders, schizophrenia, mood disorders and personality disorders. Newer atypical antipsychotics, SSRIs and mood stabilizers were increased across diagnoses while lithium and clozapine were prescribed less frequently. The rare occurrence of monotherapy in general might reflect a common trend in psychiatry fostering polydrug use. Studies of this type are biased by the fact that local habits of prescription do not allow generalisation of the findings. Such surveys should be carried out more frequently and simultaneously in different centers. Critical comparisons could help to optimize treatment.

Contribution of allelic variations in transporters to the phenotype of drug response.

Abstract: Pharmacogenomics seeks to explain the variability in drug response. Neurotransmitter transporters from the SLCA6 family are direct or indirect targets for psychotropic drugs, and their genetic variations may directly influence response to antidepressant or antipsychotic drugs. Furthermore, drug transporters located in natural barriers, such as the blood brain barrier, may influence response to psychoactive substrates. In the 5'-upstream regulatory region of the neuronal serotonin transporter lays a 44-base pair insertion/deletion polymorphism resulting in a long and a short variant. Several studies have reported a better response to selective serotonin reuptake inhibitors in individuals carrying two long alleles, however, some studies report contradictory results. Moreover, several genetic variants are known in the human norepinephrine transporter gene, and though one study reports differences in antidepressant response due to the NET G1287A polymorphism, results should be replicated by others before conclusions can be drawn. Dopamine transporters play an important role in psychotropic drug response, and a variable number of tandem repeats polymorphism in the 3'-untranslated region of the dopamine transporter gene has been studied in regards to possible correlation with antipsychotic drug response but without showing an association. P-glycoprotein has been shown to influence drug concentrations in CNS but so far, the studies on genetic polymorphisms did not show effects on the phenotype of response.Thus, several studies have looked at the influence of genetic polymorphisms on psychotropic drug response gaining different results. Best evidence exists for the serotonin transporter polymorphism influencing the response to selective serotonin reuptake inhibitors but the effects are relatively small. So far, transporter genotypes are not yet eligible for individual prediction of drug response.

The Prescription of Psychotropic Medications for Patients Discharged From a Psychiatric Emergency Service

Abstract: OBJECTIVE: Considerable debate exists about the value and wisdom of initiating "definitive" pharmacotherapies, particularly antidepressants, in the psychiatric emergency setting. We evaluated the nature and prevalence of medication prescriptions for patients discharged from an urban psychiatric emergency service and the extent to which pharmacotherapy initiation was predictive of follow-through with aftercare. METHOD: Records were reviewed for 675 consecutive individuals evaluated and discharged from a community-based psychiatric emergency service over a 3-month period (January 2003-March 2003). Information was obtained regarding diagnoses, past and current treatments, and demographic and clinical features, as well as outcomes for the subgroup of patients who received aftercare appointments within the institutional system. RESULTS: Fifty-five percent of psychiatric emergency service visits resulted in discharge, with psychotropic drug prescriptions given to about 30% of this group. Prescriptions most often included antidepressants (64%), benzodiazepines (25%), nonbenzodiazepine sedatives (20%), anti-psychotics (18%), and mood stabilizers (10%). After controlling for potential confounders, the decision to prescribe was significantly associated with a clinical diagnosis of major depressive disorder or bipolar disorder and the preexisting use of psychotropic medications. Nonprescribing occurred most often in discharged patients who had suicidal ideation, substance abuse or dependence, and an existing outpatient psychiatrist. Follow-up emergency service and new outpatient appointments were more often given to patients discharged with a prescription, but follow-through with aftercare was not more likely in this group. CONCLUSIONS: Psychiatrists in an emergency service prescribe antidepressants or other major psychotropics for about one third of discharged patients, rarely in the presence of suicidality or substance abuse or dependence, and with little evidence that initiating such medications in the emergency setting promotes more successful bridging to outpatient treatment. Language: en

Electroencephalogram slowing, sleepiness and treatment response in patients with schizophrenia during olanzapine treatment.

Abstract: Electroencephalogram (EEG) slowing is associated with clozapine side effects, e.g., sedation, and may predict treatment response during clozapine treatment. As olanzapine and clozapine share many pharmacological properties, we investigated whether EEG slowing during olanzapine treatment was related to therapy outcome and sleepiness in patients with schizophrenia. Participants were age- and gender-matched schizophrenic patients treated with olanzapine (n 54), receiving no pharmacological treatment (n 54), or cotreated with olanzapine and some other psychotropic drug (n 38). Their EEG recordings were assessed visually by the same rater blind to clinical data. The EEG scores were categorized using standardized forms. Patients with a poor treatment response did not differ significantly from those with a good response to treatment either in EEG patterns or in frequency of sleepiness. Olanzapine treatment was associated with increased rates of slow (70.4% vs. 22.3%) and sharp waves (22.2% vs. 7.4%), as well as of paroxysmal slow wave discharges (14.8% vs. 1.9%), but did not induce spike- or sharp-slow-wave complexes. Cotreatment with another antipsychotic further increased EEG abnormalities, whereas benzodiazepine administration diminished the olanzapine-induced EEG changes. The results show that olanzapine inducing both slow and sharp waves, as well as paroxysmal discharges, has a strong impact on EEG. However, as no spike- or sharp-slow-wave complexes were observed, the risk of epileptic seizure during olanzapine treatment can be regarded as low, as long as olanzapine is not combined with some other antipsychotic.

Relapse of aggressive and disruptive behavior in mentally retarded adults following antipsychotic drug withdrawal predicts psychotropic drug use a decade later.

Abstract: BACKGROUND: Mental retardation is frequently associated with aggression toward self and others. Antipsychotic medications are frequently used as a major treatment of such aggression. However, national and state policies and guidelines are weighted toward stopping or decreasing the doses of these medications whenever possible, although exceptions are permitted. The purpose of this study was to determine if relapse during or after antipsychotic drug withdrawal in mentally retarded adults predicts continuing antipsychotic drug use an average of a decade later. METHOD: We report here on a 6- to 13-year (average 10-year) follow-up of 151 institutionalized mentally retarded adults. During the period 1990-1997, the subjects had been prescribed antipsychotic medications to treat maladaptive behaviors, primarily consisting of aggression, disruptive/destructive behaviors, or a combination of these. We compared subjects' psychotropic medication profiles in 2003 as they related to outcome during the earlier period. Our goal was to determine if rapid relapse (a clinically significant increase in maladaptive target symptoms, beginning 3 months or less after antipsychotic drug termination or dosage reduction, that was reversed by antipsychotic drug reinstitution or dosage increases) during or after routine withdrawal of an antipsychotic predicted psychotropic drug use in 2003. RESULTS: For those individuals successfully withdrawn from antipsychotic medications, 66.3% (55/83) were still psychotropic drug free in 2003. For those who rapidly relapsed during the period 1990-1997 following antipsychotic drug withdrawal or dosage decreases, only 9.0% (5/55) were psychotropic medication free in 2003. CONCLUSION: These observations support policies and guidelines indicating that attempts to stop treatment with antipsychotic medications in mentally retarded individuals are worthwhile. However, the results also indicate that eventual discontinuation of antipsychotic medications in institutionalized mentally retarded adults who have previously relapsed upon such withdrawal is unlikely to be successful. Rigid adherence to drug withdrawal policies and guidelines in such individuals should be reconsidered. Language: en

In rats chronically treated with clozapine, tyrosine depletion attenuates the clozapine-induced in vivo increase in prefrontal cortex dopamine and norepinephrine levels

Abstract: We previously reported that depletion of brain tyrosine attenuated the acute clozapine (CLZ)-induced increase in medial prefrontal cortex (MPFC) dopamine (DA) levels. This effect was now examined after chronic CLZ treatment. Male rats received CLZ (10 mg kg−1 day−1) in drinking water for 21 days. On day 18, a cannula was stereotaxically implanted over the MPFC. A microdialysis probe was inserted on day 20. On day 21 after a stable baseline was reached, rats received an acute injection of vehicle (VEH) or a tyrosine- and phenylalanine-free mixture of neutral amino acid [NAA(−)] (total 1 g kg−1, i.p., two injections, 1 h apart) followed by CLZ (10 mg kg−1, i.p.) or VEH. Basal tyrosine or norepinephrine (NE) levels were not different between the groups, but basal DA was higher in the group treated chronically with CLZ (p<0.05). Acute CLZ (10 mg kg−1, i.p.) increased MPFC DA and NE levels to 370% and 510% of baseline, respectively, and similarly in rats chronically pretreated with CLZ or VEH. NAA(−) did not affect basal MPFC DA or NE levels but significantly attenuated acute CLZ-induced DA (220% of baseline) and NE (330% of baseline) levels (p<0.01) in rats pretreated chronically with CLZ or with VEH. These data demonstrate that even after chronic CLZ administration, the acute CLZ-induced increases in MPFC DA and NE levels depend on the availability of brain tyrosine. Judicious manipulation of brain tyrosine levels may provide a useful probe as well as a mechanism for enhancing psychotropic drug actions.

Novel salts of conjugated psychotropic drugs and processes of preparing same

Abstract: Novel chemical conjugates of a psychotropic drug residue and an amino-containing organic acid residue selected to reduce side effects induced by the psychotropic drug when administered per se, to enhance the therapeutic activity of the psychotropic drug and/or to exert anti-proliferative activity, in which the amino group is in the form of an acid addition salt thereof and which are characterized by high stability are disclosed. Further disclosed are processes for preparing the chemical conjugates and addition salts thereof, pharmaceutical compositions containing the chemical conjugates and methods utilizing the chemical conjugates for treating various medical conditions.

Quantifying Drug-Drug Interactions in Pharmaco-EEG

Abstract: A drug interaction refers to an event in which the usual pharmacological effect of a drug is modified by other factors, most frequently additional drugs. When two drugs are administered simultaneously, or within a short time of each other, an interaction can occur that may increase or decrease the intended magnitude or duration of the effect of one or both drugs. Drugs may interact on a pharmaceutical, pharmacokinetic or pharmacodynamic basis. Pharmacodynamic interactions arise when the alteration of the effects occurs at the site of action. This is a wide field where not only interactions between different drugs are considered but also drug and metabolites (midazolam/alpha-hydroxy-midazolam), enantiomers (ketamine), as well as phenomena such as tolerance (nordiazepam) and sensitization (diazepam). Pharmacodynamic interactions can result in antagonism or synergism and can originate at a receptor level (antagonism, partial agonism, down-regulation, up-regulation), at an intraneuronal level (transduction, uptake), or at an interneuronal level (physiological pathways). Alternatively, psychotropic drug interactions assessed through quantitative pharmaco-EEG can be viewed according to the broad underlying objective of the study: safety-oriented (ketoprofen/theophylline, lorazepam/diphenhydramine, granisetron/haloperidol), strictly pharmacologically-oriented (benzodiazepine receptors), or broadly neuro-physiologically-oriented (diazepam/buspirone). Methodological issues are stressed, particularly drug plasma concentrations, dose-response relationships and time-course of effects (fluoxetine/buspirone), and unsolved questions are addressed (yohimbine/caffeine, hydroxizyne/alcohol).

Handbook of Clinical Psychopharmacology for Therapists, 4th ed.

Abstract: This book ended up being more than I expected. I was anticipating a handy reference source for commonly used psychotropic medications, which it is, but that is only part of what makes this a useful and valuable resource tool. The Handbook of Clinical Psychopharmacology for Therapists is logically organized into 3 major sections. The first, “Understanding Psychopharmacology: The Basics,” is easily the most academic of the three. Liberal use of case histories and sidebars with interesting anecdotal information, however, make it surprisingly readable and user-friendly. The second section, “Clinical Syndromes: Etiology, Diagnosis, and Treatment Implications,” is the largest and most clinical segment. In it the reader will find a comprehensive list and description of the most common psychiatric disorders. Included in these descriptions are helpful suggestions regarding possible drugs and medical conditions that cause similar behavioral patterns as well as guidelines for when nonmedical practitioners should consider referral for medication treatment. The third section, “Medications and Pharmacologic Treatment,” contains the information that I was initially looking for. Again the authors organize their material in a logical and clinically useful manner on the basis of major drug categories. They also provide handy thumb-tabs along with numerous charts and tables relating to issues such as dose guidelines, common side effects, special considerations, and treatment algorithms. I particularly appreciate their inclusion of a review on over-the-counter and herbal products, an area of increasing interest in recent years. This third section is what will make this text a frequent reference source for me and is the reason I plan to keep it on my desk rather than in my bookcase. The book ends with 8 appendices intended for readers looking for a more in-depth discussion of topics mentioned earlier in the book. Included here are an expanded review of pharmacokinetics, numerous tables listing psychotropic drug interactions, an outline for performing a neurocognitive mental status exam, and a reference list of books to recommend to patients. All in all, the Handbook of Clinical Psychopharmacology for Therapists is a well-written text that is capable of providing the reader with comprehensive review information as well as quick reference assistance.

Use of psychotropic drugs in 0 to 5 years old children in Aquitaine (France): prevalence and associated factors.

Abstract: Purpose To describe the use of psychotropic drugs in children aged 0–5 years, in the Aquitaine region of South-west France and identify associated socio-demographic, familial and medical factors. Methods Data used in this study come from the regional drug claims database of the National Health Insurance System of Aquitaine and from postal self-questionnaires sent to parents and prescribing physicians. Results In Aquitaine, psychotropic drugs were redeemed at least once in 2002 for 3.2% of young children. Hydroxyzine, niaprazide or diazepam were claimed at least once by 2.7% of children registered in the database. Prescribers were mostly general practitioners (76.7%) and pediatricians (20.1%). Psychotropic claims were more frequent in children having the highest number of medical consultations in 2002 (more than 7: odds ratio (OR) = 1.5 [95% confidence interval (CI): 1.3–1.7]) or of drug deliveries (7–15 deliveries: OR = 1.8 [95%CI: 1.6–2.1]; more than 15 deliveries: OR = 3.2 [95%CI: 2.7–3.9]). Psychotropic claim frequency increased with age. No association of psychotropic use with parental psychotropic use, socio-professional category and familial situation was found. Conclusions Psychotropic delivery prevalence in Aquitaine in young children was below 5% in 2002. It notably concerned drugs of which the use is not devoid of toxicity because of anticholinergic properties. Copyright © 2006 John Wiley & Sons, Ltd.

Depression in pregnancy: drug safety and nursing management.

Abstract: Women who are already predisposed to depression are at increased risks during pregnancy because of endocrine changes; untreated depression in pregnant women might lead to adverse effects for both mothers and infants. This article examines outcomes associated with the use of antidepressants during pregnancy and identifies how nurses can help depressed pregnant women. It is recommended that pregnant women who have mild depression be treated with nonpharmacologic therapy, such as counseling, cognitive-behavioral therapy, or interpersonal psychotherapy. Current appropriate treatment for pregnant women with moderate and severe depression is antidepressant medication, although there is no consensus on the best antidepressants for use in pregnancy. Thus, the psychotropic drug must be chosen carefully to minimize negative effects on infants and mothers, for some studies have demonstrated deleterious effects on infants. Nurses in multiple settings who interact with pregnant women should be aware of the necessity of screening for depression. Nurses in antenatal care settings can refer appropriately screened women to mental health specialists; psychiatric nurse practitioners can identify suitable interventions based on potential risks and benefits to maternal and infant health.

Endocrine side effects among psychiatric patients treated with antipsychotics

Abstract: UNLABELLED The increased serum prolactin is one of the side effects of antipsychotic treatment. The clinical signs of its elevated level are galactorrhea, gynecomastia, breast tenderness and sexual dysfunction. These symptoms can cause poor compliance and relapse of the psychiatric illnesses. The possible clinical interventions are: 1) reduce of the dose of the psychotropic drug and/or addition of a dopamine agonist; 2) switch to another drug. The aim of our study was to evaluate the results of the switch to quetiapine in the cases of elevated prolactin with galactorrhea. METHODS AND PATIENTS Five of our patients (from the January to July in 2005) treated for more than two months with new generation antipsychotics had the symptoms of galactorrhea/breast tenderness. The diagnoses in according to ICD-10 were: schizophrenia and schizoaffective disorder. The differential-diagnostic examination were: physical, neuroimaging and laboratory including prolactin level followed up on the 4th, 8th weeks after the therapeutical intervention. RESULTS The galactorrhoea disappeared and prolactin levels normalized after the switching to quetiapine. In the case of bromocriptine addition to previous therapy symptom stopped but the hormone level did not change significantly. There was remission and/or stabilisation of psychotic symptoms with quetiapine. CONCLUSION The galactorrhea is one of the possible side effects of psychotropic drugs. We presented five patients with this kind of symptoms related to antipsychotic treatment. After the switch to quetiapine the galactorrhea and breast tenderness stopped, the level of prolactin normalized and the psychiatric condition of the patients showed remission. Our data support the benefit of the switch to another new generation drug, first of all to quetiapine, in the cases of galactorrhea and/or elevated prolactin level related to the antipsychotic pharmacotherapy.

Attitudes toward different formulations of psychotropic drugs

Abstract: Attitudes toward psychotropic drug treatment are likely to be a factor in medication adherence and outcome, but preferences regarding different drug formulations have been rarely assessed. To explore attitudes toward different drug formulations in a cross-sectional study in psychiatric patients and a comparison group of healthcare professionals. Inpatients (n = 59, age 46 ± 14 years, 63% female) and staff members (n = 96, age 40 ± 10 years, 65% female) of a psychiatric department were surveyed using a questionnaire on attitudes toward 18 possible application forms of psychotropic drugs including newer formulations such as fast-dissolving tablets. The questionnaire asked respondents to rate each option on a 6-point scale (1 being most positive), and then state which would be their preferred form of application if (hypothetically) psychopharmacological treatment was required. Attitudes were clustered and differences between patients and healthcare providers, and the influence of gender and age, were analyzed. The attitudes towards the different drug formulations in patients and staff members were nearly identical. There was a high preference for oral applications, particularly conventional tablets and capsules. Non-invasive parenteral application forms obtained intermediate attitude ratings, whereas injections were rated significantly less favorably. Gender and age had no substantial influence on the results. Attitudes toward psychotropic medications may reflect common stereotypes. The strong aversion to injections in both groups may be partly explained by pain avoidance and phobic tendencies. Given that attitudes toward treatment are likely to influence later adherence to medication long before wanted and unwanted drug effects occur, our findings should be taken into account early in the planning of psychotropic treatment. Support and/or education should be given to the patient before the first dose to encourage a positive attitude towards the planned treatment.

Application of microarray technology in psychotropic drug trials.

Abstract: Microarrays can be manufactured to detect hundreds of thousands of polymorphisms in DNA from patients in psychotropic drug trials. Some of these polymorphisms may be useful as pharmacogenetic predictors of treatment outcomes. We tested a microarray designed to detect common polymorphisms in the CYP2D6 gene that encodes debrisoquine hydroxylase (DH). DH is involved in the hepatic metabolism of many psychotropics. CYP2D6 genotypes predicted plasma steady state concentrations of nortriptyline, a classic DH substrate, in a sample of geriatric patients with major depression. However, in a sample of 246 geriatric patients treated with paroxetine or mirtazapine, both of which are metabolized in part by DH, CYP2D6 genotypes determined with microarrays did not predict discontinuations due to adverse events or severity of adverse events. For modern antidepressants such as paroxetine and mirtazapine, pharmacokinetic factors that are regulated by CYP2D6 such as plasma drug concentrations may be less important than pharmacodynamic factors in determining outcomes. Studies of single candidate genes such as CYP2D6 have only begun to utilize the potential of microarrays for pharmacogenetic prediction. Yet, there is controversy as to whether genome-wide studies designed to detect millions of genotypes with microarrays will lead to new pharmacogenetic discoveries, or whether a more focused, hypothesis-driven approach is better.

The Ecology of Mental Health Care in Taiwan

Abstract: This paper applied the ecology model of general medical care by White et al. to analysis of mental health services utilization within the National Health Insurance in Taiwan. The ambulatory and inpatient claims of a 200,000-person cohort in 2001 were analyzed. The yearly and monthly prevalence estimates included psychotropic drug prescription, diagnosis of mental disorders, psychiatric ambulatory visit and admission, community psychiatric rehabilitation, and certificate of chronic psychosis. The results revealed one-fourth of people had received psychotropic drugs during the year, mostly from non-psychiatrists. Besides, the elderly might be excessively exposed to psychotropic drugs, and community rehabilitation programs were underutilized.

Psychotropic medication consumption in the Buenos Aires general population

Abstract: OBJECTIVE The purpose of this study was to estimate the prevalence of psychotropic drug consumption among the general population of the city of Buenos Aires. METHODS A survey was conducted among 1,777 respondents in different neighborhoods of the city. RESULTS At the time of the survey 15,5% of the general population was using some kind of psychotropic medication, and life-time prevalence of use was 29,4%. Utilization was higher in woman and the elderly. There were significant consumption differences by level of educational attainment but no by social class. More than 12% of the population was using benzodiazepines and 3% antidepressants. Almost 25% of the consumers was using the medication without medical advice. Twenty five percent of the users recognized themselves as very dependent on these medications. CONCLUSIONS Psychotropic drug use is very extended among the general population of the city of Buenos Aires. Measures to restrict the irrational use of these medications and to control them adequately should be implemented.