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Current Medicinal Chemistry 2018Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a...
BACKGROUND
Serotonin reuptake inhibitors (SRIs) and cognitive-behavioral psychotherapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD). However, a significant proportion of patients do not respond satisfactorily to first-choice treatments. Several options have been investigated for the management of resistant patients.
OBJECTIVE
The aim of the present paper is to systematically review the available literature concerning the strategies for the treatment of resistant adult patients with OCD.
METHOD
We first reviewed studies concerning the definition of treatment-resistant OCD; we then analyzed results of studies evaluating several different strategies in resistant patients. We limited our review to double-blind, placebo-controlled studies performed in adult patients with OCD whose resistance to a first adequate (in terms of duration and dosage) SRI trial was documented and where outcome was clearly defined in terms of decrease in Yale-Brown Obsessive-Compulsive Scale (YBOCS) scores and/or response/ remission rates (according to the YBOCS).
RESULTS
We identified five strategies supported by positive results in placebo-controlled randomized studies: 1) antipsychotic addition to SRIs (16 RCTs, of them 10 positive; 4 head-to-head RCTs); among antipsychotics, available RCTs examined the addition of haloperidol (butyrophenone), pimozide (diphenyl-butylpiperidine), risperidone (SDA: serotonin- dopamine antagonist), paliperidone (SDA), olanzapine (MARTA: multi-acting receptor targeted antipsychotic), quetiapine (MARTA) and aripiprazole (partial dopamine agonist); 2) CBT addition to medication (2 positive RCTs); 3) switch to intravenous clomipramine (SRI) administration (2 positive RCTs); 4) switch to paroxetine (SSRI: selective serotonin reuptake inhibitor) or venlafaxine (SNRI: serotonin-norepinephrine reuptake inhibitor) when the first trial was negative (1 positive RCT); and 5) the addition of medications other than an antipsychotic to SRIs (18 RCTs performed with several different compounds, with only 4 positive studies).
CONCLUSION
Treatment-resistant OCD remains a significant challenge to psychiatrists. To date, the most effective strategy is the addition of antipsychotics (aripiprazole and risperidone) to SRIs; another effective strategy is CBT addition to medications. Other strategies, such as the switch to another first-line treatment or the switch to intravenous administration are promising but need further confirmation in double-blind studies. The addition of medications other than antipsychotics remains to be studied, as several negative studies exist and positive ones need confirmation (only 1 positive study).
Topics: Antipsychotic Agents; Cognitive Behavioral Therapy; Drug Resistance; Drug Substitution; Drug Therapy, Combination; Humans; Obsessive-Compulsive Disorder; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 29278206
DOI: 10.2174/0929867325666171222163645 -
BMC Psychiatry Jul 2015Tic disorders (TDs) are common neuropsychiatric disorders in children. Typical antipsychotics, such as haloperidol and pimozide have been prescribed to control tic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tic disorders (TDs) are common neuropsychiatric disorders in children. Typical antipsychotics, such as haloperidol and pimozide have been prescribed to control tic symptoms as first-line agents. However, adverse effects have led to the use of newer atypical antipsychotics. Aripiprazole is one of alternatives. The aim of this study was to evaluate the efficacy and safety of aripiprazole for children with TDs.
METHODS
Randomized controlled trials (RCTs), quasi-RCTs and control studies evaluating aripiprazole for children with tic disorders were identified from PubMed, Embase, Cochrane library, Cochrane Central, four Chinese database and relevant reference lists. Quality assessment referred to the Cochrane Handbook for Systematic Reviews of Interventions.
RESULTS
Twelve studies involving 935 participants were included. The general quality of included studies was poor. Only one study used placebo as a control and others used positive drug controls. Participants were aged between 4 and 18 years. The period of treatment ranged from 8 to 12 weeks. Seven studies (N = 600 patients) used the YGTSS scale as the outcome measurement, and there was no significant difference in reduction of the total YGTSS score between the aripiprazole and positive control groups (MD = -0.48, 95 % CI [-6.22, 5.26], P = 0.87, I(2) = 87 %). Meta-analysis of four of the studies (N = 285 patients) that compared aripiprazole with haloperidol showed that there was no significant difference in reduction of the total YGTSS score (MD = 2.50, 95 % CI [-6.93, 11.92], P = 0.60, I(2) = 88 %). Meta-analysis of two studies (N = 255 patients) that compared aripiprazole with tiapride showed that there was no significant difference in reduction of the total YGTSS score (MD = -3.15, 95 % CI [-11.38, 5.09], P = 0.45, I(2) = 86 %). Adverse events (AEs) were reported in 11 studies. Drowsiness (5.1 %-58.1 %), increased appetite (3.2 %-25.8 %), nausea (2 %-18.8 %) and headache (2 %-16.1 %) were common AEs.
CONCLUSION
In conclusion, aripiprazole appears to be a promising therapy for children with TDs. Further well-conducted RCTs are required to confirm this issue.
Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Child, Preschool; Haloperidol; Humans; Randomized Controlled Trials as Topic; Tic Disorders; Treatment Outcome
PubMed: 26220447
DOI: 10.1186/s12888-015-0504-z -
Canadian Journal of Psychiatry. Revue... May 2015It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T... (Review)
Review
OBJECTIVE
It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T wave (QTc) interval prolongation. We conducted a systematic review of the literature to address this important issue.
METHOD
A systematic literature search was conducted in October 2014, using MEDLINE, Embase, and PsycINFO. Studies and case reports were included if they reported QTc intervals or QTc interval changes before and after antipsychotic polypharmacy or QTc intervals in both antipsychotic polypharmacy and monotherapy groups.
RESULTS
A total of 21 articles (10 clinical trials, 4 observational studies, and 7 case reports) met inclusion criteria. The clinical trials have shown that a combination treatment with risperidone or pimozide is not obviously related to an increase in QTc interval, whereas ziprasidone or sertindole combined with clozapine may prolong QTc interval. Among the 4 observational studies, antipsychotic polypharmacy was not clearly associated with QTc prolongation in 3 studies, each cross-sectional. In contrast, one prospective study showed a significant increase in QTc interval following antipsychotic coadministration. The case reports indicated an increased risk of QTc prolongation in at least some patients receiving antipsychotic polypharmacy.
CONCLUSIONS
Currently available evidence fails to confirm that antipsychotic polypharmacy worsens QTc prolongation in general, although the evidence is scarce and inconsistent. Clinicians are advised to remain conservative in resorting to antipsychotic polypharmacy, as a combination of some QTc-prolongation liable antipsychotics may further prolong QTc interval, and efficacy supporting the clinical benefits of antipsychotic polypharmacy is equivocal, at best.
Topics: Antipsychotic Agents; Heart Rate; Humans; Polypharmacy
PubMed: 26174525
DOI: 10.1177/070674371506000503 -
Journal of the American Academy of... Jan 2015To evaluate the effect of antipsychotics on the corrected QT (QTc) interval in youth. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the effect of antipsychotics on the corrected QT (QTc) interval in youth.
METHOD
We searched PubMed (http://www.ncbi.nlm.nih.gov/pubmed) for randomized or open clinical trials of antipsychotics in youth <18 years with QTc data, meta-analyzing the results. Meta-regression analyses evaluated the effect of age, sex, dose, and study duration on QTc. Incidences of study-defined QTc prolongation (>440-470 milliseconds), QTc >500 milliseconds, and QTc change >60 milliseconds were also evaluated.
RESULTS
A total of 55 studies were meta-analyzed, evaluating 108 treatment arms covering 9 antipsychotics and including 5,423 patients with QTc data (mean age = 12.8 ± 3.6 years, female = 32.1%). Treatments included aripiprazole: studies = 14; n = 814; haloperidol: studies = 1; n = 15; molindone: studies = 3; n = 125; olanzapine: studies = 5; n = 212; paliperidone: studies = 3; n = 177; pimozide: studies = 1; n = 25; quetiapine: studies = 5; n = 336; risperidone: studies = 23; n = 2,234; ziprasidone: studies = 10, n = 523; and placebo: studies = 19, n = 962. Within group, from baseline to endpoint, aripiprazole significantly decreased the QTc interval (-1.44 milliseconds, CI = -2.63 to -0.26, p = .017), whereas risperidone (+1.68, CI = +0.67 to +2.70, p = .001) and especially ziprasidone (+8.74, CI = +5.19 to +12.30, p < .001) significantly increased QTc. Compared to pooled placebo arms, aripiprazole decreased QTc (p = .007), whereas ziprasidone increased QTc (p < .001). Compared to placebo, none of the investigated antipsychotics caused a significant increase in the incidence of the 3 studied QTc prolongation measures, but there was significant reporting bias.
CONCLUSION
Based on these data, the risk of pathological QTc prolongation seems low during treatment with the 9 studied antipsychotics in otherwise healthy youth. Nevertheless, because individual risk factors interact with medication-related QTc effects, both medication and patient factors need to be considered when choosing antipsychotic treatment.
Topics: Adolescent; Antipsychotic Agents; Child; Clinical Trials as Topic; Electrocardiography; Humans; Long QT Syndrome
PubMed: 25524787
DOI: 10.1016/j.jaac.2014.10.002