piperidines and Bipolar-Disorder

Bipolar disorder and Parkinson's disease are two distinct neurological conditions that share common features related to dopaminergic dysfunction. This article presents a comprehensive review of the existing literature to investigate the association between bipolar disorder and Parkinson's disease, focusing on the dopaminergic hypothesis and potential therapeutic options. The dopaminergic hypothesis suggests that both bipolar disorder and Parkinson's disease involve impairments in the nigrostriatal or mesolimbic dopaminergic pathways. Studies have demonstrated alterations in dopamine regulation during manic and depressive phases of bipolar disorder. Similarly, Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra, resulting in motor symptoms. Recent analyses have highlighted a predisposition to Parkinson's disease in individuals with bipolar disorder. Longitudinal studies and meta-analyses have demonstrated an increased risk of developing Parkinson's disease in patients with bipolar disorder. However, differentiating idiopathic Parkinson's disease from parkinsonism induced by medications used in bipolar disorder can be challenging. Dopamine transporter (DAT) scans can aid in making a differential diagnosis. Treatment options for patients with both bipolar disorder and Parkinson's disease are limited. Neuroleptics, commonly used to manage psychotic symptoms in Parkinson's disease, may worsen motor symptoms and have limitations in bipolar disorder patients. Clozapine has shown efficacy in treating psychosis without worsening motor symptoms. Pimavanserin, an inverse agonist of the 5-HT2A receptor can offer new opportunities. However, its efficacy in bipolar disorder patients with Parkinson's disease remains unexplored. In conclusion, the association between bipolar disorder and Parkinson's disease is supported by the involvement of the dopaminergic system in both conditions. The identification of shared mechanisms opens new avenues for potential therapeutic interventions. Further research is needed to investigate the efficacy of pimavanserin and explore other treatment options for individuals with both bipolar disorder and Parkinson's disease.

Topics: Bipolar Disorder; Dopamine; Drug Inverse Agonism; Humans; Parkinson Disease; Piperidines

Acetylcholinesterase inhibitors (AceI) and memantine might prove useful in bipolar disorder (BD) given their neuroprotective and pro-cognitive effects, as highlighted by several case reports. We aimed to systematically review the efficacy and safety of AceI and memantine across multiple outcome dimensions in BD.. Systematic PubMed and SCOPUS search until 04/17/2015 without language restrictions. Included were randomized controlled trials (RCTs), open label studies and case series of AceI or memantine in BD patients reporting quantitative data on depression, mania, psychotic symptoms, global functioning, or cognitive performance. We summarized results using a best-evidence based synthesis.. Out of 214 hits, 12 studies (RCTs=5, other designs=7, total n=422) were included. Donepezil (studies=5; treated=102 vs. placebo=21): there was strong evidence for no effect on mania and psychotic symptoms; low evidence indicating no effect on depression. Galantamine (studies=3; treated=21 vs. controls=20) (placebo=10, healthy subjects=10): there was strong evidence for no effect on mania; moderate evidence for no effect on depression; low evidence for no effect on global functioning. Memantine (studies=4; treated=152 vs. placebo=88): there was conflicting evidence regarding efficacy for mania, depression and global functioning.. Paucity of RCTs; small sample size studies; heterogeneous design, outcome and patient characteristics.. There is limited but converging evidence of no effect of AceI in BD, and conflicting evidence about memantine in BD. Too few studies of mostly medium/low quality and lacking sufficient numbers of patients in specific mood states, especially mania, contributed data, focusing solely on short-term/medium-term treatment, necessitating additional high-quality research to yield more definite results.

Topics: Adult; Bipolar Disorder; Case-Control Studies; Cholinesterase Inhibitors; Clinical Trials as Topic; Depression; Depressive Disorder; Donepezil; Evidence-Based Medicine; Excitatory Amino Acid Antagonists; Female; Galantamine; Humans; Indans; Male; Memantine; Middle Aged; Piperidines; Psychotic Disorders; Randomized Controlled Trials as Topic; Treatment Outcome

Three newer atypical antipsychotic drugs were FDA-approved in 2009 and 2010 in the following order: iloperidone, asenapine and lurasidone. The three drugs are indicated for the treatment of acute schizophrenia. Asenapine is also approved for treatment of manic or mixed episodes associated with bipolar I disorder, for the maintenance treatment of schizophrenia and as an adjunctive therapy with lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.. This review compares and contrasts the current preclinical, clinical, safety and tolerability profiles of the three newer drugs, as reported in published preclinical and clinical studies, product labels, poster presentations and press releases.. Preclinical studies have reported that the three drugs have variable affinities for a wide range of neurotransmitter receptors, and are active in animal models predictive of antipsychotic activity. Asenapine is the first antipsychotic to be administered sublingually, whereas iloperidone requires titration to minimize orthostatic hypotension. Asenapine and lurasidone are associated with dose-related akathisia, whereas iloperidone is not. The three drugs appear to have relatively benign metabolic profiles. The availability of the three novel antipsychotics should provide additional options for improved treatment of schizophrenia and other psychotic disorders.

Topics: Adult; Animals; Antipsychotic Agents; Bipolar Disorder; Dibenzocycloheptenes; Drug Approval; Heterocyclic Compounds, 4 or More Rings; Humans; Isoindoles; Isoxazoles; Lurasidone Hydrochloride; Piperidines; Schizophrenia; Thiazoles; United States; United States Food and Drug Administration

The introduction of second-generation antipsychotics (SGAs) over the past 2 decades generated considerable optimism that better antipsychotic treatments for schizophrenia and bipolar disorder were possible. SGAs offer several tolerability benefits over first-generation antipsychotics (FGAs), particularly with respect to extrapyramidal symptoms. However, SGAs can induce serious metabolic dysregulations, especially in drug-naive, first-episode, and child and adolescent populations, with olanzapine and clozapine having the highest propensity to cause these abnormalities. In this context, newer SGAs were developed to further improve the adverse effect burden of available agents. However, until now, the metabolic risk profile of the newly approved SGAs - asenapine, iloperidone, lurasidone and paliperidone (paliperidone extended release and paliperidone palmitate) - has not been compared.. The objective of this systematic review and exploratory meta-analysis was to assess the effects of asenapine, iloperidone, lurasidone and paliperidone on body weight and other metabolic parameters (cholesterol, triglycerides and glucose), as this information is relevant to guide clinical decision making.. A systematic literature search (1966-March 2012), using the Cochrane Central Register of Controlled Trials and MEDLINE, CINAHL and EMBASE databases, was conducted for randomized, placebo-controlled and head-to-head clinical trials of asenapine, iloperidone, lurasidone and paliperidone. Published and unpublished data on changes in body weight and glucose and lipid metabolism parameters were extracted. For placebo-controlled, short-term (≤12 weeks) and longer-term (>12 weeks) trials with available data on ≥7% weight increase compared with pre-treatment weight, or mean weight change with standard deviation, a formal meta-analysis was performed, estimating the pooled effect size (represented as relative risk [RR], numbers-needed-to-harm [NNH] and weighted mean difference [WMD]). An exploratory meta-analysis was also performed for the other metabolic variables (cholesterol, triglycerides and glucose). Data from active- and placebo-controlled studies were used for a pooled comparison of simple mean changes in weight, cholesterol, triglyceride and glucose levels.. Fifty-six trials (n = 21 691) in schizophrenia (N = 49, n = 19 299) or bipolar disorder (N = 7, n = 2392) were identified (asenapine: N = 9, iloperidone: N = 11, lurasidone: N = 8, paliperidone: N = 28). Most of the trials (64.3%) were of ≤12 weeks' duration. In the short-term trials, compared with placebo, a ≥7% weight increase was statistically significantly (p < 0.05) most prevalent for asenapine (5 trials, n = 1360, RR = 4.09, 95% confidence interval [CI] 2.25, 7.43, NNH = 17), followed by iloperidone (4 trials, n = 1931, RR = 3.13, 95% CI 2.08, 4.70, NNH = 11) and paliperidone (12 trials, n = 4087, RR = 2.17, 95% CI 1.64, 2.86, NNH = 20). The effect of lurasidone on body weight (6 trials, n = 1793, RR = 1.42, 95% CI 0.87, 2.29) was not statistically significant. Short-term weight gain was statistically significantly (p < 0.001) greater than placebo with iloperidone (1 trial, n = 300, +2.50 kg, 95% CI 1.92, 3.08), paliperidone (15 trials, n = 3552, +1.24 kg, 95% CI 0.91, 1.57), asenapine (3 trials, n = 751, +1.16 kg, 95% CI 0.83, 1.49), as well as with lurasidone (5 trials, n = 999, +0.49 kg, 95% CI 0.17, 0.81, p < 0.01). Sufficient meta-analysable, longer-term, weight change data were only available for asenapine and paliperidone, showing statistically significantly (p < 0.001) greater weight gain versus placebo for both drugs (asenapine, 3 trials, n = 311, +1.30 kg, 95% CI 0.62, 1.98; paliperidone, 6 trials, n = 1174, +0.50 kg, 95% CI 0.22, 0.78). Although statistically significant, in general, no clinically meaningful differences were observed between the four newly approved SGAs and placebo regarding the mean change from baseline to endpoint in cholesterol levels in short-term trials, with the exception of iloperidone for total cholesterol (1 trial, n = 300, +11.60 mg/dL, 95% CI 4.98, 18.22, p ≤ 0.001), high-density cholesterol (1 trial, n = 300, +3.6 mg/dL, 95% CI 1.58, 5.62, p < 0.001) and low-density cholesterol (1 trial, n = 300, +10.30 mg/dL, 95% CI 4.94, 15.66, p < 0.001) and with the exception of lurasidone for high-density cholesterol (5 trials, n = 1004, +1.50 mg/dL, 95% CI 0.56, 2.44, p < 0.01). Asenapine increased total cholesterol statistically significantly (p < 0.05) during longer-term treatment (1 trial, n = 194, +6.53 mg/dL, 95% CI 1.17, 11.89). Regarding triglycerides, only short-term (3 trials, n = 1152, +1.78 mg/dL, 95% CI 0.40, 3.17, p < 0.01) and longer-term treatment with paliperidone (4 trials, n = 791, -0.20 mg/dL, 95% CI -. While preliminary data suggest the lowest weight gain potential with lurasidone and potentially relevant short-term metabolic effects for asenapine and iloperidone, data are still too sparse to comprehensively evaluate the metabolic safety of the newly approved SGAs. Therefore, there is a clear need for further controlled studies to evaluate whether these agents are less problematic regarding treatment-emergent weight gain and metabolic disturbances than other currently available antipsychotics.

Topics: Antipsychotic Agents; Bipolar Disorder; Blood Glucose; Dibenzocycloheptenes; Heterocyclic Compounds, 4 or More Rings; Humans; Isoindoles; Isoxazoles; Lipid Metabolism; Lurasidone Hydrochloride; Paliperidone Palmitate; Piperidines; Pyrimidines; Randomized Controlled Trials as Topic; Schizophrenia; Thiazoles; Weight Gain

It has been long known that the frequency of overweight and obese people is higher among depressed and bipolar patients than in the general population. The marked alteration of body weight (and appetite) is one of the most frequent of the 9 symptoms of major depressive episode, and these symptoms occur during recurrent episodes of depression with a remarkably high consequence. According to studies with representative adult population samples, in case of obesity (BMI over 30) unipolar or bipolar depression is significantly more frequently (20-45%) observable. Since in case of depressed patients appetite and body weight reduction is observable during the acute phase, the more frequent obesity in case of depressed patients is related (primarily) not only to depressive episodes, but rather to lifestyle factors, to diabetes mellitus also more frequently occurring in depressed patients, to comorbid bulimia, and probably to genetic-biological factors (as well as to pharmacotherapy in case of medicated patients). At the same time, according to certain studies, circadian symptoms of depression give rise to such metabolic processes in the body which eventually lead to obesity and insulin resistance. According to studies in unipolar and bipolar patients, 57-68% of patients is overweight or obese, and the rate of metabolic syndrome was found to be between 25-49% in bipolar patients. The rate of metabolic syndrome is further increased by pharmacotherapy. Low total and HDL cholesterol level increases the risk for depression and suicide and recent studies suggest that omega-3-fatty acids possess antidepressive efficacy. Certain lifestyle factors relevant to healthy metabolism (calorie reduction in food intake, regular exercise) may be protective factors related to depression as well. The depression- and possibly suicide-provoking effect of sibutramine and rimonabant used in the pharmacotherapy of obesity is one of the greatest recent challenges for professionals and patients alike.

Topics: Anti-Obesity Agents; Antidepressive Agents; Appetite Depressants; Appetite Regulation; Bipolar Disorder; Circadian Rhythm; Cyclobutanes; Depression; Depressive Disorder, Major; Dietary Carbohydrates; Energy Intake; Ghrelin; Humans; Hypothalamo-Hypophyseal System; Insulin Resistance; Leptin; Obesity; Piperidines; Pituitary-Adrenal System; Pyrazoles; Rimonabant; Seasonal Affective Disorder; Sleep Wake Disorders; Surveys and Questionnaires; Weight Gain; Weight Loss

The role of lithium carbonate in the maintenance treatment of bipolar disorder is well established. Unfortunately, many patients fail to respond adequately to this agent or are unable to tolerate its adverse effects. Divalproex has become a commonly used alternative to lithium, but it also is ineffective or poorly tolerated in many patients. This article attempts to review the available data on maintenance therapy in bipolar disorder with a variety of anticonvulsants and antipsychotics (both conventional and novel), with reference to relevant studies in acute mania and bipolar depression as well.. Evidence on maintenance therapy and relevant acute-phase data were collected using MEDLINE database searches.. Data on maintenance therapy with agents other than lithium and divalproex are sparse, and often derived from open, uncontrolled studies. Implications and flaws of available data are discussed.. Other than lithium, there are few robust double-blind data to support the use of a variety of agents in the maintenance phase. However, uncontrolled data suggest that a number of agents merit further study.

Topics: Acetates; Amines; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Calcium Channel Blockers; Carbamazepine; Clozapine; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Donepezil; Fatty Acids, Omega-3; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Indans; Lamotrigine; Lithium Carbonate; Olanzapine; Piperazines; Piperidines; Pirenzepine; Quetiapine Fumarate; Risperidone; Thiazoles; Topiramate; Treatment Outcome; Triazines; Valproic Acid

Side effects remain one of the most important clinical issues in antidepressant therapy. Patients may not be able to take appropriate treatment or may not tolerate their medication in adequate doses or for an adequate length of time to manage their depressive illness. This article reviews the extensive safety data from 6705 patients treated with paroxetine. These data indicate that paroxetine has no significant cardiovascular effects, few significant drug interactions, and no clinically significant effects on the ECG or EEG. Furthermore, paroxetine is relatively safe in overdose and has very little anticholinergic activity. Psychomotor performance is not impaired by paroxetine and there is no evidence of any zimelidine-like hypersensitivity reactions or increase in suicidal ideation. As with other selective serotonin reuptake inhibitors (SSRIs), the most common side effect is gastrointestinal upset, especially nausea. This is usually very well tolerated and rarely leads to drug discontinuation. As with other SSRIs, monoamine oxidase inhibitors should not be prescribed concurrently or soon after discontinuing paroxetine because of the risk of a lethal interaction. Paroxetine may be less likely than currently available SSRIs to cause agitation. In general, paroxetine has a very favorable side effect profile and should be an important alternative in the medical treatment of depressive illness.

Topics: Adult; Aged; Antidepressive Agents; Bipolar Disorder; Cardiovascular System; Clinical Trials as Topic; Depressive Disorder; Drug Interactions; Electrocardiography; Female; Humans; Male; Middle Aged; Neurocognitive Disorders; Neurotransmitter Uptake Inhibitors; Paroxetine; Piperidines; Placebos; Psychomotor Performance; Sleep

Mixed mood states in bipolar disorder are difficult to treat and when present indicate worse illness trajectories. Several medications are US Food and Drug Administration approved to treat mixed episodes; however, the clinical trials have been short term and rarely reported depression response.. We conducted a 5-month open-label trial examining the tolerability and efficacy of iloperidone for bipolar disorder mixed episodes.. Mania and depression scores significantly improved over the course of the study for study completers (ie, 60%-68% improvement for manic symptoms and 41%-49% for depression symptoms). Improvements were observed early in the trial and after adjusting for concomitant medication effects. The average daily dose in completers was 15 mg. Thirty-nine percent (12/31) of the eligible sample discontinued early because of adverse effects. The adverse events most commonly associated with withdrawal were increased heart rate/palpitations (n = 5 of 12) and urinary incontinence/intense urge to urinate (n = 3 of 12).. In a subset of patients, iloperidone provides relief for classic manic, depression, and irritability symptoms associated with mixed episodes in a long-term trial. Adverse effect profiles are likely to be a major factor contributing to individualized medication use.

Topics: Adult; Antipsychotic Agents; Arrhythmias, Cardiac; Bipolar Disorder; Female; Humans; Isoxazoles; Male; Piperidines; Treatment Outcome; Urinary Incontinence; Urinary Incontinence, Urge; Young Adult

To investigate the effect of adding remifentanil to propofol used in the induction of anesthesia in efficacy, and to investigate the cognitive adverse effects of electroconvulsive therapy (ECT) in the treatment of patients with severe mania.. Thirty-eight patients' condition was diagnosed as manic episode by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and were prescribed ECT by their physicians were included in a double-blind study and were randomly allocated to receive premedication with either remifentanil-atropine (study) or saline-atropine (control). Induction of anesthesia was done with propofol (1 mg/kg) and succinylcholine (0.5 mg/kg) in all patients. Assessments included seizure duration, Young Mania Rating Scale (YMRS), Mini-Mental State Examination (MMSE), and immediate cognitive adverse effects.. Twenty-nine patients with 98 ECT sessions completed treatment. There were no differences between the 2 groups in relation to age, sex, duration of disease, weight, marital status, seizure duration, YMRS, and MMSE. However, immediate cognitive adverse effects were significantly lower in remifentanil group.

Topics: Adolescent; Adult; Algorithms; Analysis of Variance; Anesthesia; Anesthetics, Intravenous; Bipolar Disorder; Demography; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Orientation; Piperidines; Propofol; Psychiatric Status Rating Scales; Remifentanil; Sample Size; Young Adult

To determine whether donepezil is effective in enhancing cognitive functioning and instrumental activities of daily living (IADLs) in older adults with bipolar disorder.. Twelve elderly patients with bipolar I or II disorder, with evidence of mild cognitive decrements, were administered donepezil 5-10 mg daily for 3 months. Participants had cognitive and functional evaluation pre-, on-, and 3-months post donepezil administration.. Three subjects dropped out of the study. In the remaining nine subjects, no significant effects were observed in cognitive and functional measures. Seven of the nine participants asked to resume the medication after completion of the study because of the perceived beneficial effects.. In this small pilot study of older adults with bipolar disorder, acute treatment with donepezil was not associated with improvements in cognitive and IADL functioning. Given limitations of the study design, placebo effects could not be ruled out in the subjects who asked to resume donepezil.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Bipolar Disorder; Cholinesterase Inhibitors; Cognition; Cognition Disorders; Donepezil; Female; Humans; Indans; Male; Middle Aged; Neuropsychological Tests; Nootropic Agents; Pilot Projects; Piperidines; Prospective Studies; Psychiatric Status Rating Scales

Because there is a high rate of partial response to standard thymoleptic medication, novel augmentation strategies for treatment-resistant bipolar disorder are needed. In an open trial, donepezil augmentation was associated with improvement in manic symptoms in 9 of 11 subjects.. We conducted a 6-week, double-blind, placebo-controlled trial of donepezil for treatment-resistant bipolar mania. Eligible subjects had a Young Mania Rating Scale (YMRS) score of at least 15 despite two or more weeks of proven therapeutic levels of lithium or valproate. Subjects who completed the trial were eligible for an 8-week open trial of donepezil. Subjects were started on donepezil 5 mg/day and were eligible for dose increase to 10 mg/day after 4 weeks.. Twelve subjects were enrolled. Eleven subjects received at least 1 week of study medication and were included in the analysis. No subjects in the donepezil group (0/6) and 60% (3/5) in the placebo group met response criteria of >30% reduction in YMRS score (Fisher's Exact p = 0.061). YMRS scores were higher at trial endpoint in the donepezil group 20.17 (3.66) compared with the placebo group [11.20 (4.60), Z = -2.476, p = 0.01]. There were no differences at trial endpoint in Hamilton Rating Scale for Depression (HAM-D) or Brief Psychiatric Rating Scale (BPRS) scores in either the intent-to-treat or the completer analyses.. Donepezil does not appear to be an effective adjunctive treatment for refractory manic symptoms. The strength of the conclusion of this trial is limited by the possibility of a false-negative result due to the small sample.

Topics: Adult; Antimanic Agents; Bipolar Disorder; Brief Psychiatric Rating Scale; Cholinesterase Inhibitors; Donepezil; Double-Blind Method; Drug Resistance; Drug Therapy, Combination; Female; Humans; Indans; Lithium Compounds; Male; Middle Aged; Piperidines; Psychiatric Status Rating Scales; Treatment Outcome; Valproic Acid

A considerable percentage of patients with bipolar disorder do not respond or do not tolerate conventional treatment. Cholinesterase (ChE) inhibitors have been suggested to possess depressogenic and antimanic properties.. We report a case series of treatment-resistant bipolar patients (n = 11) to whom we administered the ChE inhibitor donepezil. Four patients met criteria for current manic episode, 5 for mixed episode, 1 for hypomanic episode, and 1 for major depressive episode. Donepezil was added to current medication on an openlabel basis. Ratings were based on a retrospective chart review.. Of the 11 patients, 6 (54.5%) demonstrated marked improvement (improvement in CGI-S > or = 2), 3 (27.2%) demonstrated slight improvement, 1 did not respond, and 1 did not tolerate the medication. Among those patients who had marked improvement (i.e., responders, n = 6), improvement was observed within 2 weeks or less in 5 of them (83%). Patients experienced only minor side effects.. These pilot data suggest the efficacy and safety of donepezil in the treatment of bipolar disorder. To our knowledge this is the first published report on the use of donepezil in the treatment of mood disorders. Controlled, randomized, double-blind studies are necessary to validate these preliminary observations.

Topics: Adult; Bipolar Disorder; Cholinesterase Inhibitors; Donepezil; Drug Resistance; Female; Humans; Indans; Male; Middle Aged; Pilot Projects; Piperidines; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome

Risperidone is a new-generation atypical antipsychotic agent with potent dopaminergic and serotonergic antagonist activity. Compared with traditional dopamine-blocking neuroleptics, risperidone is more effective in treating negative symptoms of schizophrenia and may be less likely to cause extrapyramidal symptoms or tardive dyskinesia. Although risperidone is marketed for the treatment of schizophrenia, its novel psychopharmacologic effects and potentially mild side effect profile suggest the possibility of other therapeutic applications. An open prospective study was undertaken to determine whether risperidone might diminish psychosis, severe agitation, or rapid cycling in patients having acute and chronic primary affective illnesses (bipolar and major depressive disorder) and to document response characteristics and side effects. Additionally, a small number of patients with refractory obsessive-compulsive disorder (OCD) without comorbid tic or delusional disorders were given open trials of risperidone added to their medication.. Outpatients who fulfilled DSM-IV criteria for bipolar I, bipolar II, or major depressive disorder and suffered from psychosis or agitation associated with their illness (N = 20) and those who had treatment-refractory DSM-IV OCD (N = 5) were started on open trials of risperidone at daily doses of 1 to 1.5 mg. Doses were adjusted upwards to a maximum of 6 mg depending on clinical response.. Seventeen (85%) of 20 patients (13 bipolar, 4 major depressive disorder) showed complete or partial improvement after treatment with risperidone doses ranging from 1 to 6 mg/day (mean = 3.5 mg). Beneficial effects included decreases in agitation, psychosis, sleep disturbance, and rapid cycling. Four patients (20%) discontinued risperidone because of intolerable side effects. Five patients with refractory OCD also showed significant symptomatic improvement after the addition of risperidone.. The findings suggest that (1) risperidone may be useful in the acute/p.r.n. and chronic treatment of psychosis, agitation, and cycling accompanying affective illness, and (2) risperidone may be useful in augmenting pharmacologic response in OCD.

Topics: Adult; Ambulatory Care; Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isoxazoles; Male; Middle Aged; Obsessive-Compulsive Disorder; Piperidines; Prospective Studies; Psychiatric Status Rating Scales; Risperidone; Treatment Outcome

In a 12-week double-blind study with 36 patients with major depressive episode (DSM-III), paroxetine (Seroxat, Aropax) showed significantly quicker onset of efficacy on the Melancholia Scale, and better tolerance than imipramine. Plasma concentration analyses showed no clear concentration-efficacy correlation in either treatment group. During long-term treatment paroxetine seemed to be superior to imipramine in preventing relapse; both treatments were well tolerated. A significant correlation between baseline plasma tryptophan: large neutral amino acids ratio and final Hamilton Rating Scale for Depression (HRSD) score and a trend towards an inverse correlation between this ratio and percentage reduction in HRSD score were seen in the paroxetine group but not in the imipramine group. In line with previous studies, these results support the hypothesis that paroxetine is an effective and well tolerated antidepressant.

Topics: Amino Acids; Antidepressive Agents; Bipolar Disorder; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Imipramine; Male; Paroxetine; Piperidines; Psychiatric Status Rating Scales; Serotonin Antagonists

The thyrotropin-releasing hormone (TRH) test was performed in 100 depressed patients, including 73 patients with a major depressive episode (MDE) according to DSM-III. Thirty-one patients subsequently received an antidepressant with a predominant serotoninergic action (indalpine or citalopram), and 27 patients received a noradrenergic antidepressant (maprotiline). The diagnostic value of the TRH test was not conclusive for any of the subgroups of depressed patients: MDE, MDE with melancholia or MDE in bipolar patients. Similarly, the value of the TRH test in the choice of antidepressant treatment according to the monoaminergic action was not convincing. These results are discussed in the light of the data of the international literature.

Topics: Adult; Aged; Bipolar Disorder; Citalopram; Depressive Disorder; Female; Humans; Male; Maprotiline; Middle Aged; Piperidines; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Recurrence; Serotonin Antagonists; Thyrotropin; Thyrotropin-Releasing Hormone

Topics: Antidepressive Agents; Bipolar Disorder; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Humans; Mianserin; Paroxetine; Piperidines; Psychiatric Status Rating Scales; Serotonin Antagonists

Indalpine 150 mg per day and mianserin 60 mg per day were compared in a double-blind study of 65 depressed out-patients: 52 patients completed the 4-week trial. At the end of four weeks there was no significant difference in antidepressant effect between the two drugs; but in the first two weeks, improvement in the mianserin-treated group was significantly greater than that in the indalpine group. The mianserin-treated group reported more side-effects of sedation (eg. drowsiness, clumsiness, heaviness of limbs etc.) and one patient on indalpine developed a mild leucopenia.

Topics: Adolescent; Adult; Aged; Antidepressive Agents; Bipolar Disorder; Clinical Trials as Topic; Depressive Disorder; Dibenzazepines; Double-Blind Method; Humans; Leukopenia; Mianserin; Middle Aged; Piperidines

Five depot neuroleptics (fluphenazinedeconoate, fluspirilene, pipothiazinepalmitate, penfluridol and perphenazine-enanthate) were compared based on clinical trials in subacute and chronic schizophrenic patients. The psychopathological symptoms were documented by means of the AMP-system. Statistical analyses showed several differences between the effects of the five substances. The AMP-system proved a useful instrument to differentiate similar drugs.

Topics: Administration, Oral; Bipolar Disorder; Catatonia; Clinical Trials as Topic; Delayed-Action Preparations; Drug Evaluation; Female; Fluorobenzenes; Fluphenazine; Hallucinations; Hostility; Humans; Hydrocarbons, Halogenated; Hypochondriasis; Injections, Intramuscular; Methods; Paranoid Disorders; Perphenazine; Piperidines; Schizophrenia; Spiro Compounds; Sulfonamides; Time Factors; Tranquilizing Agents

Topics: Bipolar Disorder; Humans; Piperidines; Psychotic Disorders; Urea

Aggressive behaviors can be considered symptoms of bipolar disorder, schizophrenia, post-traumatic stress, intermittent explosive, and personality disorders. Nociceptin/orphanin FQ (N/OFQ) is a peptide acting as endogenous ligand of the NOP receptor. Preclinical and clinical findings suggest the NOP receptor as an innovative target for the treatment of psychopathologies, such as anxiety, depression, and drug abuse. This study investigated the effects of NOP ligands and the behavioral phenotype of mice lacking the NOP receptor in an animal model of aggressiveness, the resident-intruder test. Mood stabilizers, such as valproate, lithium, and carbamazepine reduced aggressive behaviors of resident mice, while diazepam was inactive. In contrast, para-chlorophenylalanine (PCPA), an inhibitor of 5-HT synthesis, increased aggressiveness in mice. Similar to PCPA, the treatment with the NOP agonists Ro 65-6570 and AT-090 also increased aggressive behaviors. The systemic administration of the NOP antagonist SB-612111 did not modify the behavior of resident mice, but it prevented the aggressive behavior of Ro 65-6570. NOP receptor knockout mice did not display any behavioral difference compared to wild-type animals in the resident-intruder test. None of the treatments affected non-agonistic behaviors and spontaneous locomotion. In conclusion, NOP receptor agonists increased aggressiveness, while the pharmacological and genetic blockade of NOP receptor signaling did not modify agonistic behaviors. Ultimately, the aggressive profile of action of NOP agonists should be taken into account in the development of innovative psychiatric drugs targeting the NOP receptor.

Topics: Aggression; Agonistic Behavior; Animals; Anxiety; Bipolar Disorder; Carbamazepine; Cycloheptanes; Depression; Depressive Disorder; Disease Models, Animal; Fenclonine; Lithium; Male; Mice; Mice, Knockout; Nociceptin; Nociceptin Receptor; Opioid Peptides; Piperidines; Receptors, Opioid; Valproic Acid

Topics: Bipolar Disorder; Electroconvulsive Therapy; Electroencephalography; Humans; Hypertension; Hypnotics and Sedatives; Male; Middle Aged; Piperidines; Remifentanil; Seizures

Topics: Adult; Anesthetics, Dissociative; Bipolar Disorder; Comorbidity; Drug and Narcotic Control; France; Humans; Male; Piperidines; Substance Withdrawal Syndrome; Substance-Related Disorders; Young Adult

The aim was to evaluate the clinical profile and effectiveness of ECT in women. A retrospective chart review was carried out to identify female patients who had received ECT during the period September 2013-February 2015. Details regarding their sociodemographic, clinical, and treatment data were extracted from these records for the present study. The total number of patients, admitted to our psychiatry inpatient clinic during the survey period, was 802. During this period, 26 (3.24 %) female patients received ECT. Patients who received ECT were mostly in age group of 25-44 years (76.9 %). Twenty percent of patients were in the postpartum period. Psychotic disorders (46.1 %) was the most common diagnosis for which ECT was used, followed by bipolar affective disorder, current episode manic (19.2 %). At the end of ECT courses, 70 % of the patients showed good response with a CGI-I of 1 or 2, and 30 % showed minimal response with a CGI-I score of 3. The most common side effects were post-ECT confusion (15.4 %) and prolonged seizure (11.5 %). This rate of prolonged seizure was higher the rates reported in the literature. The bronchospasm related with remifentanil, post-ECT bradycardia, hypertensive crisis and oligohydramnios were also reported in one case each. ECT is a safe and effective treatment option in women with severe psychiatric disorders and disorders in the perinatal/postpartum period are a major area of ECT use. The female gender may be a contributing factor for the higher rates of prolonged seizure.

Topics: Adult; Aged; Anesthetics, Intravenous; Bipolar Disorder; Bradycardia; Bronchial Spasm; Depression, Postpartum; Depressive Disorder; Electroconvulsive Therapy; Female; Hospitals, Psychiatric; Humans; Hypertension; Middle Aged; Oligohydramnios; Piperidines; Pregnancy; Pregnancy Complications; Psychotic Disorders; Puerperal Disorders; Remifentanil; Retrospective Studies; Treatment Outcome; Turkey; Young Adult

To report a case of mania associated with the titration of donepezil in an elderly patient.. A 400-bed academic acute care psychiatric facility.. A 70-year-old male with a history of paranoid schizophrenia, alcohol dependence, and mild cognitive impairment was admitted after concerns that he was responding to internal stimuli and exhibited increased disorganization. The patient was initiated on quetiapine, titrated to 500 mg at bedtime, to address disorganization, hallucinations, and poor sleep. After improvement of psychotic symptoms and assessment of cognitive function, donepezil 5 mg daily was initiated and titrated to 10 mg daily after two weeks. Days following the increase of donepezil to 10 mg daily, the patient exhibited symptoms of mania and became hyperverbal with elevated mood and agitation. A decreased need for sleep with an increase in cleaning activities throughout the day was noted. Donepezil was suspected to have induced the new symptoms and was discontinued. Following discontinuation, the manic symptoms completely resolved over a two-week period.. The titration of donepezil was associated with the onset of mania. Previous trials involving off-label donepezil use in patients with bipolar disorder, but not schizophrenia, have reported the development of manic symptoms. Although rare, there is mounting evidence that donepezil is associated with the emergence of mania. Clinicians should be aware of this potential side effect in all patients treated with donepezil.

Topics: Aged; Bipolar Disorder; Cholinesterase Inhibitors; Cognitive Dysfunction; Donepezil; Humans; Indans; Male; Nootropic Agents; Piperidines

Topics: Adult; Bipolar Disorder; Donepezil; Humans; Indans; Male; Middle Aged; Nootropic Agents; Piperidines

Topics: Aged; Bipolar Disorder; Cholinesterase Inhibitors; Donepezil; Female; Humans; Indans; Male; Mental Disorders; Middle Aged; Piperidines

There is considerable evidence that pro-cholinergic agents can cause depressed mood. However, there are also published case reports of a rare association between cholinesterase inhibitors and mood elevation in patients with pre-existing major functional psychiatric disorders, or organic disorders other than dementia. This report adds to the literature by describing a case of mood elevation in a patient without pre-existing psychiatric disorder.

Topics: Aged; Bipolar Disorder; Cholinesterase Inhibitors; Dementia, Vascular; Donepezil; Female; Humans; Indans; Piperidines; Treatment Outcome

Topics: Antipsychotic Agents; Bipolar Disorder; Dibenzocycloheptenes; Drug Approval; Heterocyclic Compounds, 4 or More Rings; Humans; Isoxazoles; Piperidines; Safety; Schizophrenia; Treatment Outcome; United States; United States Food and Drug Administration

This article briefly reviews the novel atypical second-generation antipsychotic drugs iloperidone (Fanapt®), asenapine (Saphris®), and lurasidone (Latuda®), all of which have been approved by the U.S. Food and Drug Administration since 2009. Each is indicated for the treatment of schizophrenia, and asenapine has an additional indication for bipolar disorder. Very little information is available on their use in other disorders, pediatric and geriatric patients, and during pregnancy and breastfeeding. Their overall efficacy is no different than other antipsychotic drugs, but they do have different side effect profiles. Because of their unique pharmacologies and different tolerability profiles, they may be a more effective alternative for patients who do not respond to or cannot tolerate other antipsychotic drugs.

Topics: Adult; Aged; Antipsychotic Agents; Bipolar Disorder; Child; Clinical Trials as Topic; Dibenzocycloheptenes; Female; Heterocyclic Compounds, 4 or More Rings; Humans; Isoindoles; Isoxazoles; Lurasidone Hydrochloride; Male; Piperidines; Pregnancy; Schizophrenia; Thiazoles; Treatment Outcome

Topics: Alzheimer Disease; Antimanic Agents; Bipolar Disorder; Donepezil; Drug Interactions; Excitatory Amino Acid Antagonists; Female; Humans; Indans; Memantine; Middle Aged; Nootropic Agents; Piperidines; Psychoses, Substance-Induced

Cognitive dysfunctions are being recognized as a major roadblock to functional recovery in patients with bipolar disorders. Little is known about the treatment of these cognitive dysfunctions. Donepezil, approved to treat memory dysfunction in Alzheimer's disease, is evaluated for cognitive dysfunctions common in bipolar disorder. Of concern is some evidence that donepezil may trigger affective instability.. All bipolar disordered patients in a private practice setting treated with donepezil for memory problems were analyzed. Patients were assessed for memory improvement and change in psychiatric status with the Clinical Global Impression of Improvement Scale.. Thirty-nine of 58 patients (67%) reported improvement with a mean score of 1.82 (standard deviation+/-0.82). Nine treatments were stopped because of side effects and 4 showed no response. No bipolar I patient received benefits. Thirty-six of 43 (84%) of bipolar II patients showed improvement. Fifty percent of bipolar NOS showed improvement. Four bipolar I patients (57%), 1 bipolar II patient (2%) and 2 bipolar NOS patients (25%) stopped donepezil due to worsening affective symptoms.. This is a naturalistic case series with a single evaluator. Other medications used in treatment were changed as clinically indicated.. This case series suggests utility for donepezil in the treatment of cognitive problems associated with bipolar II disorder and bipolar disorder NOS. Bipolar I patients showed no improvement and a concerning trend to destabilize with donepezil treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bipolar Disorder; Cholinesterase Inhibitors; Cognition Disorders; Donepezil; Female; Humans; Indans; Male; Memory Disorders; Middle Aged; Patient Dropouts; Piperidines; Private Practice; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome

Topics: Bipolar Disorder; Donepezil; Humans; Indans; Male; Middle Aged; Nootropic Agents; Piperidines

Tardive dyskinesia and other delayed-onset abnormal involuntary movement disorders may occur as a result of the use of psychotropic drugs. A distinction is usually made between classic tardive dyskinesia (TD) (orobuccal-lingual-facial) and tardive dystonia, tardive tremor (TT), tardive akathisia, and other related syndromes. In spite of the development of atypical antipsychotics with fewer side effects, tardive movement disorders nevertheless continue to present a significant clinical and therapeutic challenge. Several reports have suggested that donepezil may be helpful in the treatment of TD.. A preliminary study was conducted of 7 patients (5 women and 2 men) enrolled over a period of 6 months who had been experiencing TT for a period of at least 1 year. The ages of the patients ranged from 64 to 79 years, and all patients were on stable antipsychotic therapy. Donepezil was added to their usual treatment for 8 weeks. The severity of patients' extrapyramidal symptoms was assessed using the tremor subscale of the Simpson-Angus Scale (SAS) and self-rated with a modification of the Clinical Global Impressions scale, the Subjective Clinical Improvement Impression scale. The clinical response was evaluated by comparing the rating scores at baseline prior to donepezil treatment and every 2 weeks thereafter.. The addition of donepezil (up to 10 mg/day) was associated with a clinically significant improvement (from 37.5% to 63.6%) on the SAS tremor subscale following 4 weeks of therapy. Only 1 patient discontinued follow-up due to side effects.. The results suggest that donepezil may be effective in the treatment of TT, and this finding should be evaluated further by a randomized controlled study.

Topics: Aged; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Cholinesterase Inhibitors; Cognition Disorders; Donepezil; Dyskinesia, Drug-Induced; Female; Geriatric Assessment; Hospitalization; Humans; Indans; Male; Middle Aged; Piperidines; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Treatment Outcome

We present a case of anesthesia for electroconvulsive (ECT) therapy that was complicated by emetic sensitivity to etomidate, fragile ictal threshold, and mild pseudocholinesterase deficiency. The anesthetic was designed in this patient taking all his issues in consideration. The mild pseudocholinesterase deficiency necessitated a (50-75%) reduction in succinylcholine dosage, careful monitoring of the train of four, and postictal amnestic coverage to prevent paralysis upon waking. The significant emetic response to etomidate prompted substitution to propofol and preemptive ondansetron. Propofol significantly raised the ictal threshold but significantly reduced the postprocedural emesis. Eventually, this clinical challenge was resolved with adjunctive use of low-dose etomidate and remifentanil. This combination preserved the ictal parameters, providing patient comfort, good clinical response, and therapeutic efficacy. Although seizure duration and quality often are restored with hyperventilation and caffeine, this case necessitated a return to etomidate for the restoration of satisfactory ictal parameters. Although this effect of remifentanil has been described with methohexital, and etomidate with alfentanil, to the best of our knowledge, this is the first reported case of adjunctive remifentanil with etomidate for preserving ictal threshold. The outpatient course of ECT was thus completed with all psychiatric and anesthetic goals satisfied: adequate seizure quality and duration, no paralysis upon waking, no post-ECT nausea and vomiting, and patient satisfaction. Anesthesiologists should be aware of factors influencing the seizure duration and, keeping in mind the coexisting medical conditions of the patient, adjustments should be made to get the best possible outcome.

Topics: Adult; Alcoholism; Anesthesia; Anesthetics, Intravenous; Anxiety Disorders; Bipolar Disorder; Differential Threshold; Electroconvulsive Therapy; Etomidate; Humans; Male; Piperidines; Remifentanil

Topics: Anesthetics, Intravenous; Bipolar Disorder; Drug Resistance; Drug Therapy, Combination; Electroconvulsive Therapy; Female; Humans; Methohexital; Middle Aged; Piperidines; Remifentanil; Seizures; Treatment Outcome

Topics: Aged; Bipolar Disorder; Cholinesterase Inhibitors; Depressive Disorder, Major; Donepezil; Female; Humans; Indans; Male; Piperidines

Topics: Aged; Alzheimer Disease; Bipolar Disorder; Donepezil; Female; Humans; Indans; Male; Nootropic Agents; Piperidines

Topics: Aged; Bipolar Disorder; Dementia; Donepezil; Drug Therapy, Combination; Female; Humans; Indans; Middle Aged; Nootropic Agents; Piperidines

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Chronic Disease; Female; Humans; Isoxazoles; Piperidines; Risperidone; Schizophrenia, Paranoid

Topics: Antipsychotic Agents; Bipolar Disorder; Humans; Isoxazoles; Male; Middle Aged; Neuroleptic Malignant Syndrome; Piperidines; Risperidone; Treatment Outcome

Topics: Adolescent; Aggression; Antipsychotic Agents; Bipolar Disorder; Child; Child Behavior Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Isoxazoles; Lithium; Male; Piperidines; Risperidone

Topics: Acute Disease; Adult; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Isoxazoles; Male; Piperidines; Risperidone; Treatment Outcome

Topics: Antipsychotic Agents; Bipolar Disorder; Depressive Disorder; Humans; Isoxazoles; Piperidines; Risperidone

Topics: AIDS Dementia Complex; Antipsychotic Agents; Bipolar Disorder; Humans; Isoxazoles; Male; Middle Aged; Piperidines; Risperidone

Topics: Antipsychotic Agents; Bipolar Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Humans; Isoxazoles; Lithium Carbonate; Male; Middle Aged; Neurologic Examination; Obsessive-Compulsive Disorder; Pimozide; Piperidines; Recurrence; Risperidone

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Imipramine; Male; Neuroleptic Malignant Syndrome; Penfluridol; Piperidines; Schizophrenia

Topics: Acute Disease; Antipsychotic Agents; Basal Ganglia Diseases; Bipolar Disorder; Child; Chronic Disease; Delayed-Action Preparations; Dibenzazepines; Dibenzothiepins; Dosage Forms; Drug Therapy, Combination; Fluphenazine; Humans; Paranoid Disorders; Perphenazine; Pimozide; Piperazines; Piperidines; Schizophrenia; Structure-Activity Relationship; Thioridazine; Thioxanthenes; Tranquilizing Agents

Topics: Adult; Aged; Alanine Transaminase; Bipolar Disorder; Blood Pressure; Blood Sedimentation; Butyrophenones; Creatinine; Dementia; Electrocardiography; Female; Hemoglobinometry; Humans; Leukocyte Count; Long-Term Care; Male; Middle Aged; Neurocognitive Disorders; Paranoid Disorders; Piperidines; Schizophrenia; Time Factors; Tranquilizing Agents

Topics: Adolescent; Adult; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Brain Diseases; Cerebrovascular Disorders; Child; Epilepsy; Humans; Hypertension; Hypnotics and Sedatives; Intracranial Arteriosclerosis; Middle Aged; Phenothiazines; Piperidines; Schizophrenia; Seizures

Topics: Anxiety; Bipolar Disorder; Cyclohexanes; Humans; Intelligence Tests; Lysergic Acid Diethylamide; Perception; Phencyclidine; Phenothiazines; Piperidines; Psychoses, Substance-Induced; Reaction Time; Schizophrenia; Schizophrenic Psychology; Thinking

Topics: 1-Propanol; Adjustment Disorders; Adult; Aged; Antidepressive Agents; Antiparkinson Agents; Anxiety Disorders; Basal Ganglia Diseases; Biperiden; Bipolar Disorder; Delayed-Action Preparations; Depression; Depressive Disorder, Major; Female; Humans; Mental Disorders; Middle Aged; Paranoid Disorders; Piperidines; Schizophrenia, Disorganized; Tranquilizing Agents; Tremor

Topics: 1-Propanol; Adult; Age Factors; Aged; Bipolar Disorder; Follow-Up Studies; Humans; Middle Aged; Neurologic Manifestations; Parkinson Disease; Piperidines; Psychotic Disorders; Schizophrenia; Tranquilizing Agents

Topics: Adult; Antidepressive Agents; Bipolar Disorder; Butyrophenones; Computers; Dosage Forms; Electroencephalography; Fluorine; Humans; Middle Aged; Piperidines; Schizophrenia; Sleep Stages; Trifluperidol

Topics: Antisocial Personality Disorder; Bipolar Disorder; Depression; Drug Combinations; Glycolates; Hallucinogens; Mental Disorders; Piperidines; Psychotic Disorders; Pyrrolidines; Schizophrenia; Toxicology

Topics: Antisocial Personality Disorder; Anxiety; Anxiety Disorders; Atropine; Bipolar Disorder; Depression; Drug Combinations; Drug Therapy; Electroencephalography; Glycolates; Hallucinogens; Mental Disorders; Piperidines; Psychoses, Alcoholic; Psychotic Disorders; Pyrrolidines; Schizophrenia; Toxicology

Topics: Bipolar Disorder; Butyrophenones; Hallucinations; Humans; Hypnotics and Sedatives; Intellectual Disability; Mental Disorders; Paranoid Disorders; Paresis; Parkinsonian Disorders; Piperidines; Psychomotor Agitation; Psychotic Disorders; Schizophrenia

Topics: Bipolar Disorder; Butyrophenones; Chorea; Drug Therapy; Electromyography; Haloperidol; Humans; Huntington Disease; Mental Disorders; Movement Disorders; Piperidines; Psychotic Disorders; Temperament

Topics: Bipolar Disorder; Chlorpromazine; Depression; Depressive Disorder, Major; Methylphenidate; Piperidines; Psychotic Disorders