Combination Of Psychotropic Drugs Research Articles

A pilot study on in-utero exposure to psychotropic drugs: A comparison of pharmacological classes on neonatal and maternal outcomes

ObjectiveIn this retrospective cohort study, we compared neonatal and maternal outcomes after exposure of different psychopharmacological classes of drugs. Both psychiatric diseases and pharmacological treatment of these are associated with lower birth weights, lower APGAR scores, and NICU admission. Therefore, we tried to rule out the role of psychotropics as if no differences were found between pharmacological classes, the lower birthweights might not be attributable to these. MethodWe divided our groups in exposed to atypical antipsychotic drugs, Selective Serotonin Reuptake Inhibitors (SSRI), Tricyclic Antidepressants (TCA), benzodiazepines, and different combinations of psychotropic drugs. The last group included SSRIs combined with benzodiazepines, methylphenidate, lithium, and classic antipsychotic drugs. ResultsWe used univariate regression analysis to see which factors from our rich dataset including pharmacological class, are associated with birth weight, APGAR scores, gestational age, and NICU admission. The significant associations from univariate analyses were further analyzed using ancova analysis or logistic regression where applicable. ConclusionWe found no clinically relevant differences in neonatal and maternal outcomes between the different exposed pharmacological classes. However, our dataset may have been too small to draw firm conclusions.

How potentially inapropriate are psychotropic drugs prescribing in acute psychiatric unit for the elderly? Results from a large multicentric audit in France

Adverse drug reactions (ADRs) are a major public health issue, especially when it comes to the elderly. Potentially inappropriate prescribing (PIP) are one of the causes of ADRs in older people. A PIP can be defined as a prescription for which the benefit/risk ratio is unfavourable compared to other therapeutic alternatives. Psychotropic drugs are the second highest risk class for ADRs in the elderly. In order to reduce the prevalence of PIP, prescription assistance tools have been created. An inventory of PIP of psychotropic drugs in older patients hospitalized in psychiatry units was carried out in a French regional setting in 2019. A criteria grid was established based on 2 tools: STOPP/START criteria and Laroche's list adapted to French practice. This grid targeted each class of psychotropic drugs, drugs with a high anticholinergic burden and non-recommended combinations of psychotropic drugs. Three hundred forty-seven patients were included. A high prevalence of PPI was found for each class of psychotropic drugs. The highest prevalence of PPI was found among benzodiazepines (90.3%): long-term prescription, long half-life drugs, respiratory insufficiency or cognitive impairment condition. 56.5% of the subjects had a not-recommended combination of psychotropic drugs (prescription of drugs of the same pharmacotherapeutic class), 26% had a PIP of antipsychotics: prescription for insomnia, use of phenothiazine, 11.8% of drugs with anticholinergic properties and 7.4% of antidepressants: especially prescription of tricyclic drugs. These results obtained on a large population underline the interest of considering the specificities of prescriptions in the elderly. It shows both the interest and the limits of the current criteria defining the PIP in the context of a hospitalization in psychiatry for an acute disorder in elderly subjects.

Visual compatibility and particle counter evaluations of syringes of intramuscular psychotropic coadministered solutions

BackgroundPatients in the acute phase of agitation can require the administration of multiple drugs by intramuscular injection in order to temporarily stabilise their condition. Administration of multiple psychotropic medications in...

Metformin Enhances Antidepressant/Antipsychotic Combination Therapy of Schizophrenia With Comorbid Depression in a Murine Model.

Comorbid depressive disorders confound the diagnosis and therapy of schizophrenia. Using a murine model incorporating both MK801 and chronic unpredictable mild stress exposures, we successfully replicated both psychosis and depression. Ex vivo patch clamp recordings and in vivo calcium imaging demonstrated impaired neural activity in the prefrontal cortex (PFC). We then administered triple-drug combinations consisting of two antidepressants (mirtazapine and venlafaxine) plus an antipsychotic (either clozapine or olanzapine), and found improved PFC neuronal activity and performance in behavioral assays. Moreover, the addition of metformin to both psychotropic drug combinations brought further improvements in depressive and schizophrenic-like behaviors and physiological parameters. In summary, our data modeled the neuropathophysiology of schizophrenia with comorbid depression, and may inform drug intervention strategies.

Sudden Death Associated with Complex Treatment of Acute Mania: Case Report and Toxicological Findings

Background: Antipsychotic drugs, mood-stabilizers, and sedatives are used routinely to treat acute mania, sometimes in combinations, most of which are poorly evaluated for efficacy and safety. Objective: We report a case of sudden death in a 40-year-old man with acute mania treated aggressively with combinations of drugs that resulted in in potentially toxic, high serum drug concentrations. Method: After the autopsy, analysis were conducted to determine levels of the administered medications using GC-MS and LC-MS/MS. Results: Although dosed within recommended ranges, circulating concentrations of some antipsychotic drugs given were excessive, suggesting possible pharmacokinetic interactions. In particular, valproate may have increased serum levels of haloperidol, clozapine, and promazine. The proposed cause of death was cardiac arrest, to which the high concentrations of antipsychotics may have contributed. Conclusion: This case suggests caution in the aggressive treatment of mania with combinations of psychotropic drugs and highlights the need of further clinical studies to identify consequences of drug-drug interactions of antimanic drugs, even when given at recommended doses.

Antipsychotic-induced hyperprolactinemia

IntroductionAs antipsychotic agents are increasingly used, many patients are at risk for antipsychotic-induced hyperprolactinemia.Aims of the studyEstimate the prevalence of hyperprolactinemia in patients treated by a single antipsychotic and identify the risk factors for its occurrence.MethodsThis is a prospective study carried out at the psychiatric department of psychiatry of university hospital of Mahdia during 24 months. We have included all patients with a follow up and treated by single antipsychotic for at least 12 weeks. A pituitary MRI has been requested for patients with a prolactin level higher than 100 ng/ml.ResultsWe have collected 92 patients. Hyperprolactinemia was found in 34.8% of patients among which 7.6% have had prolactin level greater than 150 ng/ml. Pituitary MRI have revealed 2 cases of macro-adenoma. The decrease of the antipsychotic doses has significantly improved prolactin levels. The switch of antipsychotic with another less inducing hyperprolactnimea has significantly decreased prolactin levels. 7 factors were correlated significantly to hyperprolactinemia: sex (female), substance use, presence of side effects, combination of psychotropic drugs, atypical antipsychotics, type of antipsychotic: Haloperidol and amisulpride, antipsychotic dose greater than 1000 mg Chlorpromazine equivalent.ConclusionHyperprolactinemia must be carefully identified, through a pre-therapeutic assessment and monitoring of patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Psychotropic Polypharmacy in Patients withDementia: Prevalence and Predictors.

Antipsychotics and other psychotropics are frequently used to treat neuropsychiatric symptoms in patients with dementia, even though the evidence for effect is limited. Concerns have been raised about the safety of antipsychotics, but concomitant use of multiple psychotropic drug classes (psychotropic polypharmacy) may also pose a risk for patients. To investigate the prevalence and predictors associated with use of psychotropic polypharmacy in patients with dementia. A population-based study using nationwide registers. Patients with dementia were identified among all Danish residents ≥65 years on January 1, 2012. Data on prescriptions and comorbidity was included in the analysis. Overlapping prescriptions for different psychotropic drug classes were used to determine psychotropic polypharmacy. A multivariable logistic regression analysis was conducted to evaluate factors independently associated with the prescription of other psychotropic drug classes among patients already using antipsychotics. Among all patients registered with dementia (34,553), 25.3% (8,728) used ≥2 psychotropic drugs. Among patients treated with antipsychotics 75.8% (5,403) used at least one other psychotropic drug during the antipsychotic treatment period. Nursing home residency, number of non-psychotropic medications used in 2011, and prior psychiatric diagnosis were associated with psychotropic polypharmacy among antipsychotic drug users. The most frequent combination of psychotropic drugs was antipsychotics and antidepressants. Concomitant use of psychotropic drugs was frequent in dementia patients. Patients living in nursing homes had the highest risk of receiving a combination of antipsychotics and other psychotropic drugs. Concomitant use of psychotropics may cause adverse events, and potential consequences for patients' safety call for further investigation.

The Density of N-Methyl-D-Aspartate Receptor in Rat Striatum Varies with Differing Psychotropic Drug Treatments

Background: A number of studies in rodents suggest that antipsychotic drug treatment can either alter the levels or functionality of the N-methyl-D-aspartate receptor (NMDAR). This raises the possibility that some of the therapeutic actions or side-effects of antipsychotic drugs could be mediated through the NMDAR. Objective: To determine if treatments with combinations of psychotropic drugs change the levels of the NMDAR in rat Central Nervous System (CNS). Methods: In situ radioligand binding and autoradiography were used to quantify [3H]MK-801 binding to NMDAR in frozen CNS sections from rats treated with vehicle, haloperidol (0.1 mg/kg/day), olanzapine (1.0 mg/kg/ day), lithium (25.5 mg/kg/day) or, at the same doses, haloperidol and lithium or olanzapine and lithium for 28 days. Results: There was a significant variation of [3H]MK-801 binding with treatment in the rat striatum due to higher levels of radioligand in rats treated with haloperidol compared to those treated with olanzapine and lithium (p < 0.01; Cohen’s d = 1.47). Levels of radioligand binding did not vary with drug treatment in the cortex. Conclusion: These data argue for some effect of polypharmacy on NMDAR levels, possibly localized to the striatum. Further studies of mood stabilisers with known effects on NMDAR functionality, such as valproate and lamotrigine, with and without antipsychotic drugs could be worthwhile as they may show a greater effect on NMDAR density in the CNS. Keywords: Glutamate, haloperidol, lithium, olanzapine, NMDA, psychotropic drug.

Increased all-cause mortality with psychotropic medication in Parkinson's disease and controls: a national register-based study.

Use of medication and polypharmacy is common as the population ages and its disease burden increases. We evaluated the association of antidepressants, benzodiazepines, antipsychotics and combinations of psychotropic drugs with all-cause mortality in patients with Parkinson's disease (PD) and a matched group without PD. We identified 5861 PD patients and 31,395 control subjects matched by age, gender and marital status, and obtained register data on medication use and vital status between 1997 and 2007. All-cause mortality was significantly higher with the use of most groups of psychotropic medication in PD patients and controls. Hazard ratios were as follows for the medication types: selective serotonin reuptake inhibitors or serotonin-noradrenalin reuptake inhibitors, PD HR=1.19, 95% CI=1.04-1.36; Control HR=1.77, 95% CI=1.64-1.91; benzodiazepines, PD HR=1.17, 95% CI=0.99-1.38; Control HR=1.39, 95% CI=1.29-1.51; benzodiazepine-like drugs, PD HR=1.33, 95% CI=1.11-1.59; Control HR=1.27, 95% CI=1.18-1.37; first-generation antipsychotics, PD HR=1.89, 95% CI=1.42-2.53; Control HR=2.12, 95% CI=1.82-2.47; second-generation antipsychotics, PD HR=1.46, 95% CI=1.20-1.76; Control HR=2.00, 95% CI 1.66-2.43; and combinations of these drugs compared with non-medicated PD patients and controls. Discontinuation of medication was associated with decreased mortality in both groups. The use of psychotropic medication in the elderly is associated with increased mortality, independent of concurrent neurodegeneration due to PD. Confounding by indication may partly explain the higher hazard ratios in medicated controls compared with medicated PD patients. Our findings indicate that neurodegeneration should not be a separate contraindication per se for the use of psychotropic drug in patients with PD, but its use should be based on careful clinical evaluation and follow-up.

The utilization of psychopharmacological treatment and medication adherence among Medicaid enrolled children and adolescents with bipolar depression

BackgroundTo examine the psychotropic medication utilization and compare adherence to treatment regimens in pediatric bipolar depression patients. Methods2003–2007 MAX data from four geographically diverse states were used. According to the regimen received by the patients (6–18 years) in the first month after the index bipolar depression diagnosis, patients were categorized into six mutually exclusive groups. The month to month change of treatment regimen in each group was then assessed during the 6 month post-index bipolar depression diagnosis. Adherence to each regimen was measured as continuation of the initial regimen, switch to a new regimen, augmentation with medication from a different therapeutic category, and discontinuation of all pharmacotherapies. Repeated measure analysis was conducted to compare the trend of each adherence measure across the study groups. ResultsOf the 5,460 subjects identified, 15.39% received antipsychotic monotherapy, 9.43% received mood stabilizer monotherapy, 5.77% received antidepressant monotherapy, 26.48% received mood stabilizer–antipsychotic polytherapy, 22.51% received antidepressant polytherapy, and 19.89% received antipsychotic–mood stabilizer–antidepressant polytherapy. At the end of the follow-up period, over 50% of the 1st month polytherapy users and less than 50% of the monotherapy users were continuing their initial regimen. Repeated measure analysis using antipsychotic monotherapy as the reference group suggested differences in trend slopes (p<0.05). LimitationsIn absence of structured clinical evaluation, bipolar disorder diagnoses cannot be ascertained in this study. ConclusionsBipolar depression patients were predominantly treated with combinations of psychotropic drugs. Potentially questionable practice, such as antidepressant monotherapy was used only in a small fraction of patients. Combination regimens had better adherence as compared to monotherapies.

Asterixis (Flapping Tremors) As an Outcome of Complex Psychotropic Drug Interaction

Asterixis (Flapping Tremors) As an Outcome of Complex Psychotropic Drug Interaction

Psychotropic Drug Treatment, Clinical Characteristics and Cognitive Processing Speed in Patients with Schizophrenia: Results from the ELAN Study

Psychotropic drug combinations (PDC) are common in the treatment of patients with schizophrenia but there is little research regarding the effects of PDC on cognition. The aim of this study was to analyse the effects of antipsychotic monotherapy and various types of PDC on cognitive processing speed (CPS). ELAN is a 24-month multi-site prospective observational controlled trial following up 374 patients with schizophrenia under routine treatment conditions following discharge from inpatient treatment. The propensity score method, multinomial logistic regression analyses and mixed effects regression models were used. CPS correlated significantly with PANSS and GAF scores and improved over time in the monotherapy group. Negative effects of some PDC (antipsychotics + tranquilizers/antipsychotics+at least 2 other psychopharmacological subclasses, sedative/anticholinergic drugs/high adjusted antipsychotic dose) lost significance after controlling for clinical characteristics. Indications for PDC should be examined with care although, in the present study, effects on cognition were small.

Bruk av psykofarmaka hos mennesker med utviklingshemning

Individuals who have mental retardation and live by themselves have little knowledge of psychotropic medication. The aim of this study is to examine the use of psychotropic medication among individuals with mental retardation, 10-20 years after they moved from institutionalised to open care. 116 individuals with mental retardation, who had moved from one specific institution to open care (in their own homes) in the period 1984-94, were included in the study. Data were collected from medical records, and from interviews with a caregiver. 50 (43%) individuals used psychotropic drugs at the time of recording. It was common to use combinations of psychotropic drugs; 37 used antipsychotics, nine used antidepressants and 14 used anxiolytics. Information on the degree of retardation was not available for all individuals; but 20 of the 28 who used antipsychotics had serious mental retardation, while eight had a mild or moderate degree of mental retardation (p < 0.001). No statistically significant association was found between degree of retardation and use of antidepressants and anxiolytics. Only 14 (27%) of those who used psychotropic drugs had a psychiatric diagnosis. The drugs were usually prescribed by a regular general practitioner. Individuals with mental retardation use psychotropic medication extensively. Caregivers' insufficient knowledge on how to apply non-pharmacological intervention may be an explanation for the extensive use of psychotropic drugs in treatment of challenging behaviour.

Specificity of mood stabilizer action on neuronal growth cones

Lithium, valproic acid (VPA) and carbamazepine (CBZ) are commonly used mood stabilizers, but their therapeutic mechanism is unclear. These drugs all cause the same morphological effects on postnatal rat neuronal dorsal root ganglia (DRG) growth cones via an inositol-reversible mechanism. However, due to limitations in earlier analysis, the effects of combining drugs, drug specificity and inositol stereoisomer specificity are unknown. We devised an improved analytical method to address these issues. Dorsal root ganglia explants were cultured individually and incubated with combinations of psychotropic drugs and inositol stereoisomers. We recorded axonal growth cone morphology and calculated growth cone area per a modified method described by Williams et al. (Nature 2002; 417: 292-295). Statistically significant changes in area were calculated using non-parametric statistical testing. (i) Lithium and VPA showed an additive effect on growth cone spreading. (ii) Among eight additional psychotropic drugs to those previously tested, only imipramine and chlorpromazine altered DRG growth cone morphology. As this effect was not reversed by myo-inositol, it arises from a different mechanism to the mood stabilizers lithium, VPA and CBZ. (iii) Myo-inositol, but not scyllo- or epi-inositol, causes a significant reversal of the lithium effect on the growth cones spreading, consistent with the inositol depletion hypothesis. These results show that lithium, VPA and CBZ are unique in causing altered neuronal morphology via myo-inositol depletion.

The patterns of use of antidepressants in Estonia in 1996

The aim of the study was to examine the patterns of antidepressant use in Estonia on different levels. In 1996 the total utilization of antidepressants in Estonia was 2.69DDD/1000/day, more than 10-fold lower than in Nordic countries. The tricyclic antidepressants (TCAs) accounted for 77% (2.08DDD/1000/day) of the antidepressant utilization. The pattern of antidepressant use in Estonia was also more restrictive, as the top five individual antidepressants in Estonia gave 96% of total utilization, in contrast to 78% in Finland. In Lääne-Virumaa County (76,007 inhabitants) 1995 prescriptions for antidepressants were identified during 1996. Psychiatrists prescribed less TCAs than other physicians: 44% and 57% of all antidepressant prescriptions, respectively. The share of selective serotonin reuptake inhibitor (SSRI) prescriptions was similar both for psychiatrists and non-psychiatrists, accounting for 38%-40%. Forty per cent of the prescriptions were prescribed for treatment of diseases other than depression. In Tartu University Psychiatry Hospital 18% of 200 randomly selected outpatients were treated by intravenous injection. The most popular antidepressants in the treatment of outpatients were amitriptyline, nortriptyline, and citalopram. Analysis of the case records of 200 randomly selected inpatients showed that 43% of inpatients were treated by intravenous infusion, 19% by intravenous injection, and 26% by intramuscular administration of antidepressants. Seventy-five per cent of inpatients and 34% of outpatients were treated with various combinations of psychotropic drugs. The most popular combination was a benzodiazepine with a tricyclic. The most popular antidepressants in the treatment of inpatients were amitriptylline, imipramine, and nortriptyline. In conclusion, the utilization of antidepressants in Estonia was significantly lower than that in the Nordic countries (Finland, Sweden, and Norway) and is indirect evidence of underdiagnosis and undertreatment of depressive disorders in Estonia.

Methadone‐related overdose deaths in South Australia, 1984‐1994: How safe is methadone prescribing?

To assess the safety of prescribing of methadone tablets and syrup in South Australia by investigating overdose deaths of patients using prescribed methadone and non-patients using illegally obtained methadone. Surveillance study of deaths related to methadone overdose, 1984-1994. Coroner's Office and the Therapeutic Goods Section of the South Australian Health Commission. Per capita prescription of methadone tablets for chronic pain in South Australia was the highest in Australia in 1994. A large increase in deaths, due mainly to methadone tablets prescribed for chronic pain, occurred in 1993-1994. Illegal diversion of methadone to non-patients was responsible for half of the deaths during these two years. Deaths from overdoses of methadone syrup prescribed in maintenance therapy for drug dependence declined from 1984 to 1994. The relative risk for patient deaths due to methadone tablets versus methadone syrup was estimated to be 7.29 (95% confidence limits, 2.15-31.48). Psychotropic drug combinations were present in 86% of deaths. The methadone syrup program for drug dependence remains relatively safe. Our data raise concerns about prescribing methadone tablets for chronic pain. Better prescriber education and accountability, patient assessment and supervision and advice to patients about concurrent use of alcohol and benzodiazepines are needed.

Combinations of psychotropic drugs are becoming less favoured in psychiatric hospitals

Combinations of psychotropic drugs are becoming less favoured in psychiatric hospitals

How primary care physicians treat psychiatric disorders: a national survey of family practitioners.

A survey of 350 family practice physicians nationwide showed that 22.6% of their patients had significant psychiatric disorders. Physicians reported treating most psychiatric problems themselves, usually through a combination of psychotropic drugs, advice, and reassurance. The results suggest that anxiolytics are more conservatively used and referrals for mental health care more often made than past studies indicate. Physicians cited patient resistance and time limitations as the most important barriers to primary care mental health treatment, followed by limited third-party payment for mental health services, poor coordination between the primary care and mental health care sectors, and insufficient training to treat psychiatric disorders.

Effects of benztropine mesylate (Cogentin) on accommodation in normal volunteers.

Previously I reported that combinations of psychotropic drugs that included benztropine mesylate (Cogentin) reduced the accommodation in prepresbyopic patients. In the present study, benztropine mesylate alone was given to paid volunteer employees in a Veterans Administration hospital. Although known side effects and lower amplitude of accommodation were noted, there was no reduction in near visual acuity. This suggests that the reduced accommodation reported in the previous study was due to a greater than linear additive effect of the combined medications.

The Treatment of Anxious/Depressive States: A Double-Blind Comparison of Medazepam with Fluphenazine/Nortriptyline

A double-blind comparison of medazepam 10 mg (‘Nobrium’) tds with fluphenazine 0·5 mg/nortriptyline 10 mg (‘Motival’) tds was conducted in general practice patients suffering from anxiety with mild depression. Patients were assessed on self-rating and Physician's Rating symptom scales, and by twenty-eight days fluphenazine/nortriptyline was shown to be superior to medazepam in relief of symptoms taken individually and as a whole, the level of significance reaching 0·1% on patients' self-ratings. A similar trend in favour of fluphenazine/nortriptyline was seen at seven days but only reached 5% significance levels for certain symptom clusters on the patient's self-ratings. The implications of these results for therapy with psychotropic drug combinations, and the treatment of psychiatric illness in general practice are discussed.