Journal of Psychopharmacology最新文献

{"title":"Challenges for switching central nervous system and psychiatric medication products: A review of the literature.","authors":"Ric M Procyshyn, Martin A Katzman, Howard C Margolese, Ofer Agid, Pierre M Blier","doi":"10.1177/02698811241301219","DOIUrl":"10.1177/02698811241301219","url":null,"abstract":"<p><strong>Background: </strong>Switching between versions of medication products happens commonly despite challenges in achieving bioequivalence and therapeutic equivalence. Central nervous system and psychiatric drugs, especially those that are technically demanding to manufacture and have complex pharmacokinetic properties, such as long-acting injectables (LAIs), pose particular challenges to bioequivalence and safe and efficacious drug switching.</p><p><strong>Aims: </strong>To assess whether drugs deemed \"bioequivalent\" are truly interchangeable in drug switching.</p><p><strong>Methods: </strong>We assessed the published literature from January 2017 through June 2023 on PubMed using the MeSH terms \"drugs, generic\" OR \"equivalency, generic\" combined with terms for different psychiatric drug classes.</p><p><strong>Results: </strong>While most of the published studies returned in the search found that switching drug products was safe and clinically comparable, data on most drug classes other than those primarily indicated in the treatment of seizure disorder were sparse. Some studies also provided evidence that real-world outcomes such as adherence and hospitalizations may also be affected by switching. In addition, a review of bioequivalence testing guidance showed inconsistency across agencies and a lack of product-specific guidance from Health Canada, which raises questions about potential claims of bioequivalence for more complex products such as LAIs.</p><p><strong>Conclusions: </strong>Overall, given the difficulty in treating mental health disorders, prescribers should be cautious when switching products and formulations in a patient who has been stabilized on a drug.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"81-91"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of psychedelics on craving in addiction: A systematic review.","authors":"Sophie-Athéna Chapron, Guilhem Bonazzi, Laura Di Lodovico, Julia de Ternay, Camille Landmann, Mikail Nourredine, Francesco Salvo, Ben Sessa, Ravi Das, Benjamin Rolland, Albert Garcia-Romeu, Marc Auriacombe","doi":"10.1177/02698811241308613","DOIUrl":"https://doi.org/10.1177/02698811241308613","url":null,"abstract":"<p><strong>Background: </strong>In the context of the need to increase treatment options for substance use disorders, recent research has evaluated the therapeutic potential of psychedelics. However, there is an incomplete understanding of psychedelics' effects on craving, a core symptom of addictive disorders and a predictor of substance use and relapse.</p><p><strong>Aims: </strong>To determine if the use of psychedelics is associated with changes in craving in humans.</p><p><strong>Methods: </strong>A systematic review of the literature, using PubMed, PsycInfo, and Scopus databases up to May 2023. We included all studies assessing any substance craving levels after psychedelic use (protocol registration number CRD42021242856).</p><p><strong>Results: </strong>Thirty-eight published articles were included, corresponding to 31 studies and 2639 participants, pertaining either to alcohol, opioid, cocaine, or tobacco use disorders. Twelve of the 31 included studies reported a significant decrease in craving scores following psychedelic use. All but two studies had methodological issues, leading to moderate to high risk of bias scores.</p><p><strong>Conclusions: </strong>Some psychedelics may show promising anti-craving effects, yet the diversity and high risk of bias of extant studies indicate that these results are to be considered with caution. Further well-controlled and larger-scale trials should be encouraged.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811241308613"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the effects of erythropoietin treatment on cortical thickness and hippocampal volume in patients with mood disorders undergoing electroconvulsive therapy: A randomized, placebo-controlled trial.","authors":"Julian Macoveanu, Jeff Zarp, Maj Vinberg, Kristoffer Brendstrup-Brix, Lars V Kessing, Martin B Jørgensen, Kamilla W Miskowiak","doi":"10.1177/02698811241301224","DOIUrl":"10.1177/02698811241301224","url":null,"abstract":"<p><strong>Background: </strong>Electroconvulsive therapy (ECT) is a highly effective treatment for severe depression. However, its utilization is limited to the most severely ill patients due to stigma, healthcare provider unfamiliarity, and concerns regarding cognitive side effects. Erythropoietin (EPO) is a promising add-on treatment during ECT due to its potential to increase neuroplasticity and cognition.</p><p><strong>Aims: </strong>To explore the effects of EPO administration on cortical thickness and hippocampal volumes.</p><p><strong>Methods: </strong>In a randomized, double-blinded, placebo-controlled trial, we previously investigated the impact of EPO (40,000 IU) versus placebo (saline) infusions on cognitive side effects of unipolar or bipolar depression patients undergoing eight ECT sessions over 2.5 weeks. This cross-sectional magnetic resonance imaging study explores the effect of EPO on cortical thickness and hippocampal volumes 3 days post-ECT in 37 of the EPO trial patients (EPO <i>n</i> = 21; placebo <i>n</i> = 16).</p><p><strong>Results: </strong>Compared to the placebo group, EPO-treated patients displayed thicker cortex in distributed regions of the right hemisphere, predominantly in the parietal and occipital areas. There were no significant group differences in the hippocampal volumes or prefrontal cortex thickness.</p><p><strong>Conclusions: </strong>EPO treatment may produce a selective increase in the right-side occipito-parietal cortical thickness. In contrast, the thickness of other cognition-relevant structures was not significantly affected. This aligns with our previously reported finding that EPO has a selective effect on autobiographical memory and associated right-side parietal activity in the absence of changes in global cognition. It remains to be investigated whether longer EPO treatment and follow-up assessment may be necessary for overt structural changes in cognition-relevant brain networks.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"164-170"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of treatment with hypnotics with suicide and attempted suicide: A nationwide cohort study.","authors":"Nikolaj Kjær Høier, Trine Madsen, Adam P Spira, Keith Hawton, Poul Jennum, Merete Nordentoft, Annette Erlangsen","doi":"10.1177/02698811241309619","DOIUrl":"10.1177/02698811241309619","url":null,"abstract":"<p><strong>Background: </strong>Hypnotics have been linked to suicidal behaviors. While existing evidence has established findings of associations, more knowledge is needed regarding benzodiazepine (BZD) and non-benzodiazepine (n-BZD) hypnotics.</p><p><strong>Aim: </strong>To examine whether individuals in treatment with hypnotics had higher rates of suicide and suicide attempts than those not in treatment.</p><p><strong>Methods: </strong>A longitudinal nationwide cohort design was applied to individual-level register data, including all individuals aged 15+ years who lived in Denmark from 1995 to 2021. Incidence rate ratios (IRR) for suicide and suicide attempts were estimated using Poisson regression models. Using the National Prescription Registry, individuals who redeemed prescriptions for hypnotics at pharmacies were identified. Death by suicide was identified in the Cause of Death Register.</p><p><strong>Results: </strong>A total of 7,311,630 individuals were observed over 122,681,369 person-years. In all, 678 males and 553 females died by suicide while in treatment with BZD, resulting in respective adjusted IRRs of 2.1 (95% CI: 1.9-2.4) and 2.6 (95% CI: 2.3-3.0), when compared to those not in treatment. A total of 1774 males and 1212 females died by suicide while in treatment with n-BZD and the adjusted IRRs were 3.4 (95% CI: 3.1-3.7) and 3.6 (95% CI: 3.4-3.9), respectively.</p><p><strong>Conclusions: </strong>While confounding by indication is likely to be a major contributor, the fact that individuals in treatment with BZD or n-BZDs had higher rates of suicide and suicide attempts when compared to those not in treatment emphasizes the need to carefully monitor their mental state.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"121-131"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Responses to clinical treatment of bipolar versus unipolar depressive episodes in women versus men.","authors":"Ross John Baldessarini, Alessandro Miola, Gustavo Vázquez, Leonardo Tondo","doi":"10.1177/02698811241292946","DOIUrl":"10.1177/02698811241292946","url":null,"abstract":"<p><strong>Background: </strong>Whether responses to treatment of major depressive episodes differ between women and men or with bipolar (BD) and major depressive disorders (MDD) remains unresolved.</p><p><strong>Aims: </strong>To test for diagnostic and sex differences in responses to treatment of depression.</p><p><strong>Methods: </strong>We compared changes in the 21-item Hamilton Depression Rating Scale (HDRS₂₁) ratings of depression (<i>n</i> = 3243) between women (64.7%) and men, and between DSM-5-TR BD ([<i>n</i> = 253] and subtypes I [BD1] vs II [BD2]) and MDD (<i>n</i> = 2990), using bivariate comparisons and multivariate modeling.</p><p><strong>Results: </strong>Treatments included clinically individualized use of antidepressants (by 92.4%, in doses averaging 90.0 mg/day imipramine-equivalent), sometimes with mood-stabilizing agents (32.1%), second-generation antipsychotics (18.8%), or psychotherapy (38.6%). Depression ratings decreased by 60.6% to a final mean HDRS score of 7.44; response rate (⩾50% reduction in HDRS) averaged 63.7%. Outcomes were very similar in women and men as well as with BD versus MDD, and between BD subtypes. Moreover, age, duration of illness, initial HDRS score, dose of antidepressant, and weeks of treatment, as well as sex and diagnosis were not associated with improvement of HDRS with treatment. Only 6/42 comparisons involving 21 individual HDRS items differed significantly in improvement between sexes or diagnoses. Results were very similar to the Montgomery-Åsberg Depression Rating Scale depression ratings. Only 2.0% of the subjects experienced mood-switching into clinical (hypo)mania and the final Young Mania Rating Scale ratings averaged 0.63.</p><p><strong>Conclusions: </strong>Responses to clinical treatment (as % reduction of HDRS score, response rate, or final HDRS score) of depressed women versus men, and BD (including BD1 vs BD2) versus MDD were substantial and very similar.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"171-175"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing of erythropoietin as a neuroprotective agent against methotrexate-induced neurotoxicity in rats.","authors":"Nadine C Sabry, Haidy E Michel, Esther T Menze","doi":"10.1177/02698811241295379","DOIUrl":"10.1177/02698811241295379","url":null,"abstract":"<p><strong>Background: </strong>Methotrexate (MTX) is a cytotoxic drug that can trigger neurotoxicity via enhancing oxidative stress, apoptosis, and inflammation. On the other hand, erythropoietin (EPO) functions as an antioxidant, anti-apoptotic, and anti-inflammatory agent, in addition to its hematopoietic effects.</p><p><strong>Aim: </strong>The present study was developed to examine the neuroprotective impact of EPO against MTX-provoked neurotoxicity in rats.</p><p><strong>Methods: </strong>Chemo fog was elicited in Wistar rats via injection of one dosage of MTX (20 mg/kg, i.p) on the sixth day of the study. EPO was injected at 500 IU/kg/day, i.p for 10 successive days.</p><p><strong>Results: </strong>MTX triggered memory and learning impairment as evidenced by Morris water maze, passive avoidance, and Y-maze cognitive tests. In addition, MTX induced oxidative stress as evident from the decline in hippocampal Nrf2 and HO-1 levels. MTX brought about apoptosis, as demonstrated by the elevation in p53, caspase-3, and Bax levels, as well as the decrease in Bcl2 levels. MTX also decreased Beclin-1, an autophagy-related marker, and increased P62 expression. In addition, MTX downregulated Sirt-1/AKT/FoxO3a pathway and increased miRNA-34a gene expression. Moreover, MTX increased acetylcholinesterase activity and reduced neurogenesis. EPO administration remarkably counteracted MTX-induced molecular and behavioral disorders in rat hippocampi.</p><p><strong>Conclusion: </strong>Our findings impart preclinical indication for repurposing of EPO as a promising neuroprotective agent through modulating miRNA-34a, autophagy, and the Sirt-1/FoxO3a signaling pathway.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"147-163"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between paraoxonase-1 activity and therapeutic drug monitoring indicators in schizophrenia patients treated with olanzapine: A cross-sectional study.","authors":"Tzu-Hua Wu, Shu-Chin Hu, Nailis Sylfa, Jiahn-Haur Liao, Ahmad Raza, Bi-Li Chen, Chun-Hsin Chen, Mong-Liang Lu","doi":"10.1177/02698811241311459","DOIUrl":"10.1177/02698811241311459","url":null,"abstract":"<p><strong>Objective: </strong>Therapeutic drug monitoring (TDM) indicators have been suggested to predict overall outcome responses to olanzapine (OLZ) treatments in terms of efficacy and metabolic syndrome. This study aimed to investigate whether paraoxonase-1 (PON-1) activity can be used to predict schizophrenia patient outcomes.</p><p><strong>Methods: </strong>Schizophrenic patients (<i>N</i> = 50) aged between 20 and 65 years who received OLZ treatment were recruited, and their Positive and Negative Syndrome Scale scores, PON-1 activity, and olanzapine drug levels normalized by dose (OLZ/D) and its metabolite N-desmethyl-olanzapine (DMO), together with biochemical parameters, were determined.</p><p><strong>Results: </strong>PON-1 activity and OLZ/D were significantly correlated in 50 patients (correlation coefficient, <i>r</i> = 0.355; <i>p</i> = 0.0115). There was also a statistically significant correlation between the ratio of PON-1 activity normalized by homocysteine (Hcy) and OLZ/D (correlation coefficient <i>r</i> = 0.361; <i>p</i> = 0.01) and a significant negative correlation between the ratio of PON-1 activity normalized by Hcy and triglyceride/high-density lipoprotein (TG/HDL; correlation coefficient <i>r</i> = -0.328; <i>p</i> = 0.02).</p><p><strong>Conclusions: </strong>PON-1 activity can be used as an alternative tool for monitoring TDM through the measurement of OLZ together with its metabolite, DMO, to identify patients who have higher activity. Those who show an optimal response or who have lower activity might have greater cardiometabolic risk under long-term olanzapine treatment. Longitudinal monitoring is warranted to confirm such observations.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"141-146"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antipsychotic polypharmacy and high-dose antipsychotic therapy compared to antipsychotic monotherapy at standard doses in schizophrenia - a systematic review.","authors":"Christopher Lawrence, Chloe Roberts, Chloe Galides, Samuel R Chamberlain, Ruihua Hou","doi":"10.1177/02698811241303652","DOIUrl":"10.1177/02698811241303652","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia is considered to have a lifetime prevalence of around 1%. Up to 30% of patients diagnosed with schizophrenia are subsequently categorised as treatment resistant. Current guidelines advise against the use of antipsychotic polypharmacy (APP) or high-dose antipsychotic therapy (HDAT) in the treatment of schizophrenia; however, these treatment approaches continue to be used in up to 25% of cases.</p><p><strong>Aims: </strong>This review was to evaluate the evidence for the efficacy and tolerability of APP and HDAT as an alternative to antipsychotic monotherapy at standard doses in the treatment of schizophrenia.</p><p><strong>Methods: </strong>This is a systematic review. We searched PubMed, EMBASE and PsycINFO, for eligible trials published prior to 24 March 2023. The protocol was registered on PROSPERO (CRD42023408785). Quality assessment was conducted using the Revised Cochrane risk-of-bias tool for randomised trials.</p><p><strong>Results: </strong>A total of 14 studies were included in this review. Two studies demonstrated clinically significant improvement with APP compared to standard treatment. There was no clear evidence that APP or HDAT is definitively less tolerable than antipsychotic monotherapy at a standard dose.</p><p><strong>Conclusions: </strong>This review found limited evidence for the efficacy of APP and HDAT in the treatment of schizophrenia over the use of antipsychotic monotherapy at a standard dose. The relative tolerability was unclear. Management of treatment-resistant schizophrenia remains a prominent clinical issue and further research, including high-quality large-scale Randomised Controlled Trials (RCTs) of APP and HDAT in patients who have been unresponsive to clozapine, would be of significant benefit to the field of psychiatry.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"132-140"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficacy of vortioxetine in the acute treatment of major depressive disorder: A systematic review and meta-analysis.","authors":"Isabella Berardelli, Elena Rogante, Federico Formica, Riccardo Iannazzo, Attilio Valerio Mammoliti, Raffaele Riccioni, Skender Veizi, Roger S McIntyre, Maurizio Pompili","doi":"10.1177/02698811241309612","DOIUrl":"10.1177/02698811241309612","url":null,"abstract":"<p><strong>Background: </strong>Among the available pharmacological treatments for acute major depressive disorder (MDD), vortioxetine, a serotonin transporter inhibitor (SERT), has been widely used for its multimodal action on serotonin neurotransmission, which produces essential changes also on glutamate, gamma amino butyric acid (GABA), norepinephrine, acetylcholine, and dopamine.</p><p><strong>Aim: </strong>This systematic review and meta-analysis aimed to evaluate the acute efficacy of vortioxetine across multiple dosing and to evaluate whether there is a dose-response effect and as well there is a dose-response issue with respect to side effects in acute depression.</p><p><strong>Methods: </strong>According to PRISMA guidelines, we systematically searched three major electronic databases (PubMed/MEDLINE, PsycINFO, and Cochrane Central Register of Controlled Trials) for Randomized Controlled Trial (RCT) studies published between January 2013 and April 2024. Twenty-four studies were included in the review and two meta-analyses were conducted to determine whether the mean Montgomery-Asberg Depression Rating Scale (MADRS) scale values in the placebo groups differ significantly from the mean MADRS scale values in the group receiving vortioxetine 10 mg or vortioxetine 20 mg.</p><p><strong>Results: </strong>Vortioxetine significantly improved acute depression severity, anxiety symptoms, and cognitive function, with high response and remission rates in acute MDD. It was also well tolerated with a relatively low occurrence of severe or serious treatment-emergent adverse events (TEAEs). Observing the results of the meta-analysis, the effect was significant for both vortioxetine 10 and 20 mg, with a greater effect size for vortioxetine 20 mg.</p><p><strong>Conclusion: </strong>Vortioxetine should be considered efficacious as a first- and second-line therapy.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"92-105"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study).","authors":"R Hamish McAllister-Williams, Nicola Goudie, Lumbini Azim, Victoria Bartle, Michael Berger, Chrissie Butcher, Thomas Chadwick, Emily Clare, Paul Courtney, Lyndsey Dixon, Nichola Duffelen, Tony Fouweather, William Gann, John Geddes, Sumeet Gupta, Beth Hall, Timea Helter, Paul Hindmarch, Eva-Maria Holstein, Ward Lawrence, Phil Mawson, Iain McKinnon, Adam Milne, Aisling Molloy, Abigail Moore, Richard Morriss, Anisha Nakulan, Judit Simon, Daniel Smith, Bryony Stokes-Crossley, Paul Ra Stokes, Andrew Swain, Adeola Taiwo, Zoë Walmsley, Christopher Weetman, Allan H Young, Stuart Watson","doi":"10.1177/02698811241309622","DOIUrl":"10.1177/02698811241309622","url":null,"abstract":"<p><strong>Background: </strong>Options for 'treatment-resistant bipolar depression' (TRBD) are limited. Two small, short-term, trials of pramipexole suggest it might be an option.</p><p><strong>Aims: </strong>To evaluate the clinical effectiveness and safety of pramipexole in the management of TRBD.</p><p><strong>Methods: </strong>A multi-centre randomised, double-blind controlled trial including participants ⩾18 years old with TRBD (failure to respond, tolerate or clinical contraindication/patient refusal of ⩾2 of quetiapine, olanzapine, lamotrigine or lurasidone) randomised 1:1 to pramipexole (max 2.5 mg/day salt weight) or placebo added to ongoing mood stabiliser (<i>n</i> = 39). Primary outcome: Quick Inventory of Depressive Symptoms, Self-rated (QIDS-SR) at 12 weeks. Up to 48 weeks follow-up.</p><p><strong>Results: </strong>Pramipexole (<i>n</i> = 18) was associated with a greater reduction in QIDS-SR score at 12 weeks versus placebo (<i>n</i> = 21, 4.4 (4.8) vs 2.1 (5.1)): a medium sized (<i>d</i> = -0.72) but not statistically significant difference (95% CI: -0.4 to 6.3, <i>p</i> = 0.087). Similarly, there was a non-significant approximate 2-point (<i>d</i> = -0.76) improvement in pleasure at 6 weeks (95% CI: -0.11 to 4.20). Significant advantages of pramipexole on QIDS-SR score (6.28 points: 95% CI: 1.85-10.71) and psychosocial function (5.36 points: 95% CI: 0.38-10.35) were seen at 36 weeks post-randomisation, and on the response (46% vs 6%; <i>p</i> = 0.026) and remission (31% vs 0%; <i>p</i> = 0.030) rates at trial exit (48 weeks or last available data after 16 weeks for those affected by the early study closure). Hypomania ratings were significantly higher at 12 weeks. Otherwise, pramipexole was well tolerated.</p><p><strong>Conclusions: </strong>Clinically large, but statistically non-significant, effects of pramipexole on depression at 12 weeks, with significant longer-term benefits on mood and function were observed. Pramipexole use was complicated by dose titration and increased hypomanic symptoms. The small sample size limits interpretation. Furthermore, larger randomised placebo-controlled trials are warranted.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"106-120"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}