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Current Neuropharmacology 2019Obsessive-compulsive disorder (OCD) is associated with affective and cognitive symptoms causing personal distress and reduced global functioning. These have considerable... (Review)
Review
BACKGROUND
Obsessive-compulsive disorder (OCD) is associated with affective and cognitive symptoms causing personal distress and reduced global functioning. These have considerable societal costs due to healthcare service utilization.
OBJECTIVE
Our aim was to assess the efficacy of pharmacological interventions in OCD and clinical guidelines, providing a comprehensive overview of this field.
METHODS
We searched the PubMed database for papers dealing with drug treatment of OCD, with a specific focus on clinical guidelines, treatments with antidepressants, antipsychotics, mood stabilizers, off-label medications, and pharmacogenomics.
RESULTS
Prolonged administration of selective serotonin reuptake inhibitors (SSRIs) is most effective. Better results can be obtained with a SSRI combined with cognitive behavioral therapy (CBT) or the similarly oriented exposure and response prevention (ERP). Refractory OCD could be treated with different strategies, including a switch to another SSRI or clomipramine, or augmentation with an atypical antipsychotic. The addition of medications other than antipsychotics or intravenous antidepressant administration needs further investigation, as the evidence is inconsistent. Pharmacogenomics and personalization of therapy could reduce treatment resistance.
CONCLUSIONS
SSRI/clomipramine in combination with CBT/ERP is associated with the optimal response compared to each treatment alone or to other treatments. New strategies for refractory OCD are needed. The role of pharmacogenomics could become preponderant in the coming years.
Topics: Antidepressive Agents; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Cognitive Behavioral Therapy; Combined Modality Therapy; Drug Therapy, Combination; Guidelines as Topic; Humans; Obsessive-Compulsive Disorder; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 30101713
DOI: 10.2174/1570159X16666180813155017 -
The Psychiatric Clinics of North America Sep 2014Obsessive-compulsive disorder (OCD) affects up to 2.5% of the population of the course of a lifetime and produces substantial morbidity. Approximately 70% of patients... (Review)
Review
Obsessive-compulsive disorder (OCD) affects up to 2.5% of the population of the course of a lifetime and produces substantial morbidity. Approximately 70% of patients can experience significant symptomatic relief with appropriate pharmacotherapy. Selective serotonin reuptake inhibitors are the mainstay of pharmacological treatment. These drugs are typically used at higher doses and for longer periods than in depression. Proven second-line treatments include the tricyclic clomipramine and the addition of low-dose neuroleptic medications. OCD refractory to available treatments remains a profound clinical challenge.
Topics: Combined Modality Therapy; Drug Therapy, Combination; Humans; Nonprescription Drugs; Obsessive-Compulsive Disorder; Precision Medicine; Psychotherapy; Psychotropic Drugs
PubMed: 25150568
DOI: 10.1016/j.psc.2014.05.006 -
Lancet (London, England) Apr 2018Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments... (Comparative Study)
Comparative Study Meta-Analysis Review
Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.
BACKGROUND
Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide in adults. Pharmacological and non-pharmacological treatments are available; however, because of inadequate resources, antidepressants are used more frequently than psychological interventions. Prescription of these agents should be informed by the best available evidence. Therefore, we aimed to update and expand our previous work to compare and rank antidepressants for the acute treatment of adults with unipolar major depressive disorder.
METHODS
We did a systematic review and network meta-analysis. We searched Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS database, MEDLINE, MEDLINE In-Process, PsycINFO, the websites of regulatory agencies, and international registers for published and unpublished, double-blind, randomised controlled trials from their inception to Jan 8, 2016. We included placebo-controlled and head-to-head trials of 21 antidepressants used for the acute treatment of adults (≥18 years old and of both sexes) with major depressive disorder diagnosed according to standard operationalised criteria. We excluded quasi-randomised trials and trials that were incomplete or included 20% or more of participants with bipolar disorder, psychotic depression, or treatment-resistant depression; or patients with a serious concomitant medical illness. We extracted data following a predefined hierarchy. In network meta-analysis, we used group-level data. We assessed the studies' risk of bias in accordance to the Cochrane Handbook for Systematic Reviews of Interventions, and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. Primary outcomes were efficacy (response rate) and acceptability (treatment discontinuations due to any cause). We estimated summary odds ratios (ORs) using pairwise and network meta-analysis with random effects. This study is registered with PROSPERO, number CRD42012002291.
FINDINGS
We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo, with ORs ranging between 2·13 (95% credible interval [CrI] 1·89-2·41) for amitriptyline and 1·37 (1·16-1·63) for reboxetine. For acceptability, only agomelatine (OR 0·84, 95% CrI 0·72-0·97) and fluoxetine (0·88, 0·80-0·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1·30, 1·01-1·68). When all trials were considered, differences in ORs between antidepressants ranged from 1·15 to 1·55 for efficacy and from 0·64 to 0·83 for acceptability, with wide CrIs on most of the comparative analyses. In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32). 46 (9%) of 522 trials were rated as high risk of bias, 380 (73%) trials as moderate, and 96 (18%) as low; and the certainty of evidence was moderate to very low.
INTERPRETATION
All antidepressants were more efficacious than placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the analysis, whereas there was more variability in efficacy and acceptability in head-to-head trials. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.
FUNDING
National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.
Topics: Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Evidence-Based Medicine; Humans; Network Meta-Analysis; Patient Dropouts; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29477251
DOI: 10.1016/S0140-6736(17)32802-7 -
CNS Drug Reviews 2001The novel antidepressant mirtazapine has a dual mode of action. It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonizing the... (Review)
Review
The novel antidepressant mirtazapine has a dual mode of action. It is a noradrenergic and specific serotonergic antidepressant (NaSSA) that acts by antagonizing the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors as well as by blocking 5-HT2 and 5-HT3 receptors. It enhances, therefore, the release of norepinephrine and 5-HT1A-mediated serotonergic transmission. This dual mode of action may conceivably be responsible for mirtazapine's rapid onset of action. Mirtazapine is extensively metabolized in the liver. The cytochrome (CYP) P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4 are mainly responsible for its metabolism. Using once daily dosing, steady-state concentrations are reached after 4 days in adults and 6 days in the elderly. In vitro studies suggest that mirtazapine is unlikely to cause clinically significant drug-drug interactions. Dry mouth, sedation, and increases in appetite and body weight are the most common adverse effects. In contrast to selective serotonin reuptake inhibitors (SSRIs), mirtazapine has no sexual side effects. The antidepressant efficacy of mirtazapine was established in several placebo-controlled trials. In major depression, its efficacy is comparable to that of amitriptyline, clomipramine, doxepin, fluoxetine, paroxetine, citalopram, or venlafaxine. Mirtazapine also appears to be useful in patients suffering from depression comorbid with anxiety symptoms and sleep disturbance. It seems to be safe and effective during long-term use.
Topics: Animals; Antidepressive Agents, Tricyclic; Drug Interactions; Humans; Mianserin; Mirtazapine
PubMed: 11607047
DOI: 10.1111/j.1527-3458.2001.tb00198.x -
Journal of Veterinary Internal Medicine 2023Erroneous thyroid function test results can occur because of drugs that alter thyroid hormone physiology in one or more aspects, including synthesis, secretion,... (Review)
Review
Erroneous thyroid function test results can occur because of drugs that alter thyroid hormone physiology in one or more aspects, including synthesis, secretion, distribution, and metabolism. Research since publication of the last review in the Journal of Veterinary Internal Medicine (JVIM) 20 years ago has evaluated the effects of amiodarone, zonisamide, inhalant anesthetics, clomipramine, trilostane, and toceranib on thyroid function tests in the dog. In addition, recent work on the effects of glucocorticoids, sulfonamides, phenobarbital, and nonsteroidal anti-inflammatory drugs will be reviewed. Awareness of these effects is necessary to avoid misdiagnosis of hypothyroidism and unnecessary treatment.
Topics: Dogs; Animals; Thyroid Function Tests; Hypothyroidism; Thyroid Hormones; Amiodarone; Anti-Arrhythmia Agents; Dog Diseases
PubMed: 37498128
DOI: 10.1111/jvim.16823 -
Journal of Sleep Research Dec 2021Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based... (Review)
Review
BACKGROUND AND PURPOSE
Narcolepsy is an uncommon hypothalamic disorder of presumed autoimmune origin that usually requires lifelong treatment. This paper aims to provide evidence-based guidelines for the management of narcolepsy in both adults and children.
METHODS
The European Academy of Neurology (EAN), European Sleep Research Society (ESRS), and European Narcolepsy Network (EU-NN) nominated a task force of 18 narcolepsy specialists. According to the EAN recommendations, 10 relevant clinical questions were formulated in PICO format. Following a systematic review of the literature (performed in Fall 2018 and updated in July 2020) recommendations were developed according to the GRADE approach.
RESULTS
A total of 10,247 references were evaluated, 308 studies were assessed and 155 finally included. The main recommendations can be summarized as follows: (i) excessive daytime sleepiness (EDS) in adults-scheduled naps, modafinil, pitolisant, sodium oxybate (SXB), solriamfetol (all strong); methylphenidate, amphetamine derivatives (both weak); (ii) cataplexy in adults-SXB, venlafaxine, clomipramine (all strong) and pitolisant (weak); (iii) EDS in children-scheduled naps, SXB (both strong), modafinil, methylphenidate, pitolisant, amphetamine derivatives (all weak); (iv) cataplexy in children-SXB (strong), antidepressants (weak). Treatment choices should be tailored to each patient's symptoms, comorbidities, tolerance and risk of potential drug interactions.
CONCLUSION
The management of narcolepsy involves non-pharmacological and pharmacological approaches with an increasing number of symptomatic treatment options for adults and children that have been studied in some detail.
Topics: Adult; Cataplexy; Child; Humans; Modafinil; Narcolepsy; Sleep; Sodium Oxybate
PubMed: 34173288
DOI: 10.1111/jsr.13387 -
British Journal of Pharmacology Jul 2007New data on the pharmacology of tricyclic antidepressants (TCAs), their affinities for human cloned CNS receptors and their cytochrome P450 enzyme inhibition profiles,... (Comparative Study)
Comparative Study Review
New data on the pharmacology of tricyclic antidepressants (TCAs), their affinities for human cloned CNS receptors and their cytochrome P450 enzyme inhibition profiles, allow improved deductions concerning their effects and interactions and indicate which of the TCAs are the most useful. The relative toxicity of TCAs continues to be more precisely defined, as do TCA interactions with selective serotonin reuptake inhibitors (SSRIs). TCA interactions with monoamine oxidase inhibitors (MAOIs) have been, historically, an uncertain and difficult question, but are now well understood, although this is not reflected in the literature. The data indicate that nortriptyline and desipramine have the most pharmacologically desirable characteristics as noradrenaline reuptake inhibitors (NRIs), and as drugs with few interactions that are also safe when coadministered with either MAOIs or SSRIs. Clomipramine is the only available antidepressant drug that has good evidence of clinically relevant serotonin and noradrenaline reuptake inhibition (SNRI). These data assist drug selection for monotherapy and combination therapy and predict reliably how and why pharmacodynamic and pharmacokinetic interactions occur. In comparison, two newer drugs proposed to have SNRI properties, duloxetine and venlafaxine, may have insufficient NRI potency to be effective SNRIs. Combinations such as sertraline and nortriptyline may therefore offer advantages over drugs like venlafaxine that have fixed ratios of SRI/NRI effects that are not ideal. However, no TCA/SSRI combination is sufficiently safe to be universally applicable without expert knowledge. Standard texts (e.g. the British National Formulary) and treatment guidelines would benefit by taking account of these new data and understandings.
Topics: Animals; Antidepressive Agents, Tricyclic; Central Nervous System; Cytochrome P-450 Enzyme System; Drug Interactions; Drug Therapy, Combination; Humans; Monoamine Oxidase Inhibitors; Practice Guidelines as Topic; Selective Serotonin Reuptake Inhibitors
PubMed: 17471183
DOI: 10.1038/sj.bjp.0707253 -
Health Technology Assessment... Jun 2016Obsessive-compulsive disorder (OCD) is a relatively common and disabling condition. (Meta-Analysis)
Meta-Analysis Review
A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive-compulsive disorder in children/adolescents and adults.
BACKGROUND
Obsessive-compulsive disorder (OCD) is a relatively common and disabling condition.
OBJECTIVES
To determine the clinical effectiveness, acceptability and cost-effectiveness of pharmacological and psychological interventions for the treatment of OCD in children, adolescents and adults.
DATA SOURCES
We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Trials Registers, which includes trials from routine searches of all the major databases. Searches were conducted from inception to 31 December 2014.
REVIEW METHODS
We undertook a systematic review and network meta-analysis (NMA) of the clinical effectiveness and acceptability of available treatments. Outcomes for effectiveness included mean differences in the total scores of the Yale-Brown Obsessive-Compulsive Scale or its children's version and total dropouts for acceptability. For the cost-effectiveness analysis, we developed a probabilistic model informed by the results of the NMA. All analyses were performed using OpenBUGS version 3.2.3 (members of OpenBUGS Project Management Group; see www.openbugs.net ).
RESULTS
We included 86 randomised controlled trials (RCTs) in our systematic review. In the NMA we included 71 RCTs (54 in adults and 17 in children and adolescents) for effectiveness and 71 for acceptability (53 in adults and 18 in children and adolescents), comprising 7643 and 7942 randomised patients available for analysis, respectively. In general, the studies were of medium quality. The results of the NMA showed that in adults all selective serotonin reuptake inhibitors (SSRIs) and clomipramine had greater effects than drug placebo. There were no differences between SSRIs, and a trend for clomipramine to be more effective did not reach statistical significance. All active psychological therapies had greater effects than drug placebo. Behavioural therapy (BT) and cognitive therapy (CT) had greater effects than psychological placebo, but cognitive-behavioural therapy (CBT) did not. BT and CT, but not CBT, had greater effects than medications, but there are considerable uncertainty and methodological limitations that should be taken into account. In children and adolescents, CBT and BT had greater effects than drug placebo, but differences compared with psychological placebo did not reach statistical significance. SSRIs as a class showed a trend for superiority over drug placebo, but the difference did not reach statistical significance. However, the superiority of some individual drugs (fluoxetine, sertraline) was marginally statistically significant. Regarding acceptability, all interventions except clomipramine had good tolerability. In adults, CT and BT had the highest probability of being most cost-effective at conventional National Institute for Health and Care Excellence thresholds. In children and adolescents, CBT or CBT combined with a SSRI were more likely to be cost-effective. The results are uncertain and sensitive to assumptions about treatment effect and the exclusion of trials at high risk of bias.
LIMITATIONS
The majority of psychological trials included patients who were taking medications. There were few studies in children and adolescents.
CONCLUSIONS
In adults, psychological interventions, clomipramine, SSRIs or combinations of these are all effective, whereas in children and adolescents, psychological interventions, either as monotherapy or combined with specific SSRIs, were more likely to be effective. Future RCTs should improve their design, in particular for psychotherapy or combined interventions.
STUDY REGISTRATION
The study is registered as PROSPERO CRD42012002441.
FUNDING DETAILS
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adolescent; Adult; Antidepressive Agents; Behavior Therapy; Child; Cognitive Behavioral Therapy; Cost-Benefit Analysis; Humans; Interatrial Block; Models, Econometric; Network Meta-Analysis; Obsessive-Compulsive Disorder; Quality-Adjusted Life Years; State Medicine; United Kingdom
PubMed: 27306503
DOI: 10.3310/hta20430