Bipolar Disorder and Comorbid Use of Illicit Substances

Substance use disorders (SUD) are highly prevalent in bipolar disorder (BD) and significantly affect clinical outcomes. Incidence and management of illicit drug use differ from alcohol use disorders, nicotine use of behavioral addictions. It is not yet clear why people with bipolar disorder are at higher risk of addictive disorders, but recent data suggest common neurobiological and genetic underpinnings and epigenetic alterations. In the absence of specific diagnostic instruments, the clinical interview is conducive for the diagnosis. Treating SUD in bipolar disorder requires a comprehensive and multidisciplinary approach. Most treatment trials focus on single drugs, such as cannabis alone or in combination with alcohol, cocaine, or amphetamines. Synopsis of data provides limited evidence that lithium and valproate are effective for the treatment of mood symptoms in cannabis users and may reduce substance use. Furthermore, the neuroprotective agent citicoline may reduce cocaine consumption in BD subjects. However, many of the available studies had an open-label design and were of modest to small sample size. The very few available psychotherapeutic trials indicate no significant differences in outcomes between BD with or without SUD. Although SUD is one of the most important comorbidities in BD with a significant influence on clinical outcome, there is still a lack both of basic research and clinical trials, allowing for evidence-based and specific best practices.

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Thought overactivation as a marker of bipolar disorder

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.547 ◽

2016 ◽

Vol 33 (S1) ◽

pp. s222-s223 ◽

Cited By ~ 2

Author(s):

M. Ferrari ◽

P. Ossola ◽

V. Lucarini ◽

V. Accardi ◽

C. De Panfilis ◽

...

Keyword(s):

Bipolar Disorder ◽

Mood Disorders ◽

Subjective Experience ◽

Small Sample Size ◽

Mental States ◽

Small Sample ◽

Bipolar Spectrum ◽

Global Functioning ◽

Competing Interest ◽

Bipolar Patients

IntroductionRecent studies have underlined the importance of considering the form of thoughts, beyond their content, in order to achieve a better phenomenological comprehension of mental states in mood disorders. The subjective experience of thought overactivation is an important feature of mood disorders that could help in identifying, among patients with a depressive episode, those who belong to the bipolar spectrum.ObjectivesPatients with a diagnosis of bipolar disorder (BD) were compared with matched healthy controls (HC) on a scale that evaluates thought overactivation.AimsValidate the Italian version of a scale for thought overactivation (i.e. STOQ) in a sample of bipolar patients.MethodsThirty euthymic BD and 30 HC completed the Subjective Thought Overactivation Questionnaire (STOQ), the Ruminative Responses Scale (RRS), the Beck Depression Inventory-II (BDI-II) and global functioning (VGF).ResultsThe 9-items version of the STOQ has been back translated and its internal consistency in this sample was satisfactory (alpha = .91). Both the brooding subscore of RRS (b-RRS) (r = .706; P < .001) and STOQ (r = .664; P < .001) correlate significantly with depressive symptoms whereas only the first correlate with VGF (r = –.801; P < .001). The two groups did not differed in the b-RRS (HC = 8.41 vs BD = 9.72; P = .21), whereas BD where significantly higher in the STOQ total score (HC = 6.62 vs. BD = 14.9; P = .007).ConclusionOur results, although limited by the small sample size, confirm the validity of the STOQ and suggest that this scale could grasp a feature characteristic of BD, independently from their tendency to ruminate. The latter seems to impact more on global functioning.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Fiscal Decentralization and Public Investment in Innovation: A Country Panel Analysis

Publius The Journal of Federalism ◽

10.1093/publius/pjz033 ◽

2019 ◽

Vol 50 (4) ◽

pp. 672-697 ◽

Cited By ~ 1

Author(s):

Daniel G Colombo ◽

Jorge Martinez-Vazquez

Keyword(s):

Knowledge Spillovers ◽

Fiscal Decentralization ◽

Small Sample Size ◽

Public Investment ◽

Empirical Support ◽

Basic Research ◽

Small Sample ◽

Net Income ◽

Potential Link ◽

The Government

Abstract This article presents a first analysis of the potential link between the level of fiscal decentralization of a country and its public investment in innovation. We present a theoretical model where a “benevolent government” invests in research and development (R&D) aiming at maximizing net income, and R&D results are subject to interregional knowledge spillovers. The model predicts that decentralization leads to a lower level of public spending on innovation, and to a lower share of basic research in the government R&D budget. These hypotheses are empirically tested using country aggregate data. The results provide empirical support to the mentioned hypotheses, as we find evidence that higher levels of both expenditure and revenue decentralization are associated with a lower intensity of basic research in public R&D and with a lower level of R&D spending. The strength of the evidence, however, is weakened by the small sample size and shortcomings of the indicators used in the analysis.

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Pharmacogenetic Tests in Reducing Accesses to Emergency Services and Days of Hospitalization in Bipolar Disorder: A 2-Year Mirror Analysis

Journal of Personalized Medicine ◽

10.3390/jpm9020022 ◽

2019 ◽

Vol 9 (2) ◽

pp. 22 ◽

Cited By ~ 2

Author(s):

Camilla Callegari ◽

Celeste Isella ◽

Ivano Caselli ◽

Nicola Poloni ◽

Marta Ielmini

Keyword(s):

Bipolar Disorder ◽

Cost Saving ◽

Emergency Services ◽

Small Sample Size ◽

Economic Value ◽

Small Sample ◽

Control Group ◽

First Year ◽

Potential Cost ◽

Related Group

Despite the enormous costs associated to mood disorders’, few studies evaluate potential cost saving from the use of pharmacogenetic tests (PGT). This study compares 12 months before the execution of the PGT versus 12 months after, in terms of number and days of hospitalization and accesses to emergency services, in a sample of 30 patients affected by bipolar disorder. Secondarily, the study gives an economic value to the data based on the diagnosis-related group (DRG). Patients included in the study were required to be aged ≥18 years, sign an informed consent, have a score of Clinical Global Impression item Severity (CGIs) ≥3, and have a discordant therapy compared to the PGT in the 12 months preceding it and a therapy consistent with it for the following 12 months. Cost saving has been evaluated by paired t-tests in a mirror analysis. Statistically significant differences in all the comparisons (p < 0.0001) emerged. Important cost saving emerged after the use of PGT (€148,920 the first year versus €39,048 the following year). Despite the small sample size and lack of a control group in this study, the potential role of PGT in cost saving for the treatment of bipolar disorder treatment emerged. To confirm this result, larger and clinical trials are needed.

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Does the efficacy of asenapine in bipolar disorder increase in the presence of comorbidity with a substance use disorder? A naturalistic study

Therapeutic Advances in Psychopharmacology ◽

10.1177/2045125316674698 ◽

2016 ◽

Vol 7 (2) ◽

pp. 67-77 ◽

Cited By ~ 8

Author(s):

Sergio De Filippis ◽

Ilaria Cuomo ◽

Georgios D. Kotzalidis ◽

Daniela Pucci ◽

Pietro Zingaretti ◽

...

Keyword(s):

Bipolar Disorder ◽

Substance Use ◽

Substance Use Disorder ◽

Repeated Measures ◽

Rating Scale ◽

Type I ◽

Open Label ◽

Young Mania ◽

Psychiatric Rating ◽

Psychiatric Rating Scale

Background: Asenapine is a second-generation antipsychotic approved in Europe for treating moderate-to-severe manic episodes in adults affected by type I bipolar disorder (BD-I). We aimed to compare its efficacy in psychiatric inpatients with BD-I, with or without substance use disorder (SUD). Methods: We administered flexible asenapine doses ranging from 5–20 mg/day to 119 voluntarily hospitalized patients with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) BD-I diagnosis, with or without SUD. Patients were assessed with clinician-rated questionnaires [i.e. Brief Psychiatric Rating Scale (BPRS), Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and Global Assessment of Functioning (GAF)]. Assessments were carried out at baseline (T0, prior to treatment), and 3 (T1), 7 (T2), 15 (T3), and 30 days (T4) after starting treatment for all clinical scales and at T0 and T4 for the GAF. Results: Patients improved on all scales ( p < 0.001) across all timepoints, as shown both by paired-sample comparisons and by applying a repeated-measures, generalized linear model (GLM). Patients without comorbid SUD showed greater reductions in BPRS scores at T2 and T3, greater reduction in YMRS scores at T3, and lower HARS scores at all timepoints. HDRS scores did not differ between the two groups at any timepoint. However, the reduction in HARS scores in the comorbid group was stronger than in the BD-I only group, albeit not significantly. Side effects were few and mild-to-moderate. Conclusions: The open-label design and the relatively short observation period may expose to both type I and type II statistical errors (false positive and false negatives). Asenapine showed effectiveness and safety in hospitalized BD-I patients. Its effect was stronger in patients without comorbid SUD.

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Long-Acting Injectable Antipsychotic Treatment in Schizophrenia and Co-occurring Substance Use Disorders: A Systematic Review

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.808002 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alexandria S. Coles ◽

Dunja Knezevic ◽

Tony P. George ◽

Christoph U. Correll ◽

John M. Kane ◽

...

Keyword(s):

Systematic Review ◽

Substance Use ◽

Substance Use Disorders ◽

Case Series ◽

Small Sample ◽

Antipsychotic Treatment ◽

Opioid Use ◽

Open Label ◽

Effective Treatment Option ◽

Long Acting

Objectives: Co-occurring substance use disorders (SUDs) among individuals with schizophrenia are a prevalent and complex psychiatric comorbidity, which is associated with increased symptom severity, worsened illness trajectory and high rates of treatment non-adherence. Recent evidence suggests that the use of long-acting injectable (LAI) antipsychotics may provide an effective treatment option for individuals with this dual-diagnosis.Methods: A systematic review of the literature was conducted using the databases PubMed, PsychInfo and Google Scholar for English-language studies, investigating the use of LAIs in co-occurring schizophrenia and substance use disorders (SCZ-SUDs).Results: Eight reports [one case study (n = 1), one case series (n = 8), three open-label retrospective studies (n = 75), and three randomized controlled trials (n = 273)] investigated the use of LAI antipsychotics in 357 participants with SCZ-SUDs [alcohol use disorder: 5 studies, n = 282; cocaine use disorder: 5 studies, n = 85; amphetamine use disorder: 1 study, n = 1; cannabis use disorder: 3 studies, n = 160; opioid use disorder: 3 studies, n = 19; methylenedioxymethamphetamine (MDMA) use disorder: 2 studies, n = 9; ketamine use disorder: 1 study, n = 4] and were included in this systematic review. Findings indicate significant improvements in substance use related outcomes across 7 of 8 studies, while in 6 of 8 studies, significant improvements in psychopathology-related outcomes were reported.Conclusions: LAI antipsychotics may be an efficacious intervention option for the treatment of SCZ-SUDs. However, varying methodological rigor, generally small sample sizes and heterogeneity of samples, settings, substances of abuse, tested LAIs and comparators, as well as psychosocial cotreatments and level of reported detail across studies requires that these findings be considered preliminary and interpreted with caution. Further research is required to better understand the effects of LAIs among individuals with SCZ-SUDs.

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Evidence generation for the clinical impact of myCOPD in patients with mild, moderate and newly diagnosed COPD: a randomised controlled trial

ERJ Open Research ◽

10.1183/23120541.00460-2020 ◽

2020 ◽

Vol 6 (4) ◽

pp. 00460-2020

Author(s):

Michael G. Crooks ◽

Jack Elkes ◽

William Storrar ◽

Kay Roy ◽

Mal North ◽

...

Keyword(s):

Randomised Controlled Trial ◽

Usual Care ◽

Small Sample Size ◽

Controlled Trial ◽

Small Sample ◽

Self Management ◽

Open Label ◽

Management Interventions ◽

Randomised Controlled ◽

The Impact

Self-management interventions in COPD aim to improve patients' knowledge, skills and confidence to make correct decisions, thus improving health status and outcomes. myCOPD is a web-based self-management app known to improve inhaler use and exercise capacity in individuals with more severe COPD.We explored the impact of myCOPD in patients with mild–moderate or recently diagnosed COPD through a 12-week, open-label, parallel-group, randomised controlled trial of myCOPD compared with usual care. The co-primary outcomes were between-group differences in mean COPD assessment test (CAT) score at 90 days and critical inhaler errors. Key secondary outcomes were app usage and patient activation measurement (PAM) score.Sixty patients were randomised (29 myCOPD, 31 usual care). Groups were balanced for forced expiratory volume in 1 s (FEV1 % pred) but there was baseline imbalance between groups for exacerbation frequency and CAT score. There was no significant adjusted mean difference in CAT score at study completion, −1.27 (95% CI −4.47–1.92, p=0.44) lower in myCOPD. However, an increase in app use was associated with greater CAT score improvement. The odds of ≥1 critical inhaler error was lower in the myCOPD arm (adjusted OR 0.30 (95% CI 0.09–1.06, p=0.061)). The adjusted odds ratio for being in a higher PAM level at 90 days was 1.65 (95% CI 0.46–5.85) in favour of myCOPD.The small sample size and phenotypic difference between groups limited our ability to demonstrate statistically significant evidence of benefit beyond inhaler technique. However, our findings provide important insights into associations between increased app use and clinically meaningful benefit warranting further study in real world settings.

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An open-label, multicenter, phase II study of ceritinib in patients with advanced ALK+ non-lung solid tumors and hematological malignancies (ASCEND-10).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.3520 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 3520-3520

Author(s):

Victor Moreno ◽

Tae Min Kim ◽

Sun Young Rha ◽

Federico Longo ◽

Sith Sathornsumetee ◽

...

Keyword(s):

Antitumor Activity ◽

Solid Tumors ◽

Hematological Malignancies ◽

Small Sample Size ◽

Stage Iv ◽

Small Sample ◽

Gamma Glutamyl Transferase ◽

Efficacy And Safety ◽

Open Label ◽

Glutamyl Transferase

3520 Background: Prior studies have confirmed the efficacy and safety of ceritinib in patients (pts) with advanced ALK+ non-small cell lung cancer (Soria, et al, Lancet 2017; Shaw et al, Lancet Oncol 2017; Cho et al, JTO 2019). Ceritinib also demonstrated antitumor activity in pediatric pts with ALK+ inflammatory myofibroblastic tumor (IMT) and ALCL (Georger et al, ASCO 2015 [abstract#10005]). Long-term clinical benefits of ceritinib treatment were shown in pts with anaplastic large cell lymphoma (ALCL) (Richly et al, Blood 2015). The aim of the current study was to examine ceritinib efficacy and safety in pts with advanced ALK+ non-lung solid tumors and hematological malignancies. Methods: In this open-label, multi-arm, phase 2 (NCT02465528) trial, adult pts with ALK gene abnormalities who had received ≥1 prior systemic therapy were administered oral ceritinib 750 mg/day, under fasted conditions. Primary endpoint: investigator assessed disease control rate (DCR); secondary endpoints: investigator assessed overall response rate (ORR), duration of response (DOR), time to response (TTR), progression-free survival (PFS), and safety. Results: Overall, 22 pts (ALCL [n = 1], IMT [n = 4], glioblastoma multiforme [GBM, n = 12] and others [n = 5]) were enrolled; median (m) age: 52.5 years; male: 50%; Stage ≥IV: 95.4%. Key efficacy results are shown in the Table. mTTR in pts with confirmed complete response (CR) or partial response (PR) [n = 4] was 7.4 (range, 6–25) weeks. mDOR was not reached. mPFS (95% CI) was 2.6 (1.6, 3.7) weeks. Most common adverse events (AEs; ≥30%) were: diarrhea and nausea (59.1% each), vomiting (50.0%) and increased alanine aminotransferase (31.8%). Most common grade ≥3 AEs (≥10%): hyperglycemia (18.2%), increased gamma-glutamyl transferase, thrombocytopenia, and anemia (13.6% each). Clinical trial information: NCT02465528 . Conclusions: Ceritinib 750 mg/day under fasted conditions showed antitumor activity in pts with ALK+ ALCL and IMT; however, data interpretation is limited due to the small sample size. Safety findings were consistent with the known ceritinib safety profile. [Table: see text]

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Obsessive-Compulsive Disorder: An Open-Label Pilot Trial of Escitalopram

CNS Spectrums ◽

10.1017/s1092852900021258 ◽

2007 ◽

Vol 12 (7) ◽

pp. 519-524 ◽

Cited By ~ 10

Author(s):

Amanda Galvão-de Almeida ◽

Lucas C. Quarantini ◽

Cristianne R. Góis ◽

Rogério Santos-Jesus ◽

Ângela M.A. Miranda-Scippa ◽

...

Keyword(s):

Treatment Response ◽

Obsessive Compulsive Disorder ◽

Selective Serotonin Reuptake Inhibitors ◽

Small Sample Size ◽

Pilot Trial ◽

Small Sample ◽

Obsessive Compulsive ◽

Open Label ◽

Compulsive Disorder ◽

Axis I

ABSTRACTIntroduction: Selective serotonin reuptake inhibitors are considered the most effective and well-established pharmacotherapy for the treatment of obsessive-compulsive disorder (OCD), a chronic and disabling condition. However, ~40% of patients do not have a significant improvement, suggesting that new medications are needed. This study was designed to investigate the treatment response to escitalopram in OCD patients.Methods: This open-label study involved 11 adult OCD outpatients diagnosed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders. Data were collected and the treatment response was assessed by an experienced psychiatrist by using the Yale-Brown Obsessive-Compulsive Scale. Subjects received escitalopram 30 mg/day for 12 weeks starting at 10 mg/day. Dosage adjustments were made within 2 weeks, depending on the tolerability of the patient.Results: Six of the 11 patients (54.5%) presented a reduction of at least 40% in the baseline total Yale-Brown Obsessive-Compulsive Scale scores.Conclusion: Despite the small sample size and the open-label nature of this trial, these data suggest that escitalopram may be a useful option for patients with OCD.

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Use of paliperidone in bipolar disorder

European Psychiatry ◽

10.1016/s0924-9338(11)72867-x ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1162-1162

Author(s):

M.C. Campos Mangas ◽

M.A. Ruiz Feliu

Keyword(s):

Bipolar Disorder ◽

Partial Response ◽

Mental Health Center ◽

Small Sample Size ◽

Combined Treatment ◽

Small Sample ◽

New Drugs ◽

Response To Treatment ◽

Positive Contribution ◽

Prevention Of Relapse

IntroductionIn recent years have seen significant advances in the treatment of bipolar disorder with the appearance of new drugs such as atypical antipsychotics. However, there is still a therapeutic challenge to effectively cover the prevention of relapse.The appearance of new drugs such as paliperidone with demonstrated successful experience in the field of schizophrenia can expect the use of this drug in usual clinical setting like positive contributionObjectivesThe aim of this study is to evaluate the efficacy and safety results after 6 months of combined treatment with paliperidone in patients diagnosed with bipolar disorderMethodsThis study is an observational retrospective of the effectiveness of paliperidone as adjunctive therapy in a sample of 11 patients with bipolar disorder I treated as outpatients in a mental health center.Paliperidone addiction was caused by lack of efficacy or partial response to treatment. Scundary effects were collected during the study periodResultsIn all cases except two, was added paliperidone because of partial response to the treatment. After six months of treatment only one patient discontinued treatment due to problems of tolerability and another for lack of efficacy. The mean dose of paliperidone used was 5.7 mg / day. The addition of paliperidone significantly improved affective symptomatology.ConclusionsPharmacological treatment combined with paliperidone is effective and quite well tolerated in patients with bipolar disorder. The limitations of our study (small sample size, open study) do need more research and the realization of controlled clinical trials to confirm these findings.

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DOP75 Efficacy of tofacitinib dose escalation to 10 mg BID in patients with UC after completing maintenance therapy in remission and losing response: Data from OCTAVE open-label, long-term extension study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.114 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S112-S113 ◽

Cited By ~ 1

Author(s):

D T Rubin ◽

M C Dubinsky ◽

J Panés ◽

D C Wu ◽

N Lawendy ◽

...

Keyword(s):

Dose Escalation ◽

Small Sample Size ◽

Mucosal Healing ◽

Small Sample ◽

Extension Study ◽

Open Label ◽

Post Dose ◽

Mayo Score ◽

Kaplan Meier

Abstract Background Tofacitinib is an oral, small-molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib were demonstrated in patients with moderate to severe UC in three Phase 3 studies.1 Here, we investigated outcomes in a subpopulation of the ongoing, open-label, long-term extension study (OLE) (OCTAVE Open; NCT01470612; May 2019; database not locked), including maintenance of remission patients receiving tofacitinib 5 mg twice daily (BID) who were dose-escalated to 10 mg BID due to flare. Methods Analysis included the maintenance remission–dose-escalation subpopulation: patients who achieved remission at Week 52 in OCTAVE Sustain (tofacitinib 5 or 10 mg BID, or placebo), entered OLE (5 mg BID), but were dose-escalated to 10 mg BID due to flare (based on total Mayo score [MS]; local read endoscopy). Remission: total MS ≤2 with no subscore >1, and rectal bleeding (RB) subscore 0. Dose escalation during OLE was permitted if patients experienced a flare, defined as ≥3 increase from maintenance study baseline total MS and ≥1 increase in RB and endoscopic subscore (ES; unless ES=3 at baseline and remained 3) after ≥8 weeks of treatment in OLE. Kaplan–Meier for estimation of time to dose escalation was assessed in all OLE maintenance remission population relative to OLE baseline. Partial MS remission (≤2 with no subscore >1; no ES) assessed at Months (M)3, 6, 9 and 12 post-dose-escalation; mucosal healing (MH; ES ≤1) and remission assessed at M12 post-dose-escalation. Adverse events (AEs) also assessed. Results Of the 944 patients enrolled in OLE, 162 were in remission at baseline and received tofacitinib 5 mg BID, and 41 were dose-escalated to 10 mg BID due to flare (22 had prior TNFi failure). The cumulative proportion of patients with dose escalation was 4.3%, 10.6%, 12.6% and 13.2% at M3, 6, 9 and 12 of OLE, respectively. Partial MS remission was 75.0% at M3, and partial MS remission, MH and remission were 95.0%, 63.6% and 57.6%, respectively, at M12 post-dose escalation (Table). One case each of serious infection, herpes zoster (non-serious; opportunistic infection) and malignancy were reported (see Table). Conclusion For patients with moderate to severe UC who entered OLE in remission, received tofacitinib 5 mg BID but flared and were dose-escalated to 10 mg BID, response was recaptured for most by M3 post-dose-escalation and remission was recaptured in the majority by M12. Safety in this subpopulation was generally consistent with that observed in the overall tofacitinib UC programme.2 Due to the small sample size and open-label nature, results should be interpreted with caution. References

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