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1.
BJU Int ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33793040

RESUMO

OBJECTIVES: To investigate a novel methodology and explore whether artificially reducing the depth of penetration during intercourse matters to women. STUDY DESIGN AND METHODS: A study with a single-case experimental design ('n of 1'), in which a heterosexual couple act as their own control and the study is then replicated in subsequent couples, was conducted. Thirty-five couples were assessed for eligibility to participate. Twenty-nine couples without any sexual problems were randomized and 12 submitted sufficient data to analyse. As a proxy for reducing penis length, we artificially reduced the depth of penetration by using different sizes of silicone rings around the base of the man's erect penis. The main outcome measures were provided by the female partner on a scale of 0-100 and comprised: degree of (i) overall sexual pleasure; (ii) sexual pleasure from intercourse alone; and (iii) emotional connection to the male partner. The female partner was also asked before the experiment began to rate the degree of positive or negative change that would be personally meaningful for her. RESULTS: On average, reducing the depth of penetration led to a statistically significant 18% reduction of overall sexual pleasure with an average 15% reduction in length of the penis. The longer the erect penis, the less likely the rings were to have an impact on sexual pleasure. There was a range of individual responses, however, with a minority of women reporting that reducing the depth of penetration was more pleasurable on some occasions. CONCLUSIONS: Size may matter in women in a healthy stable relationship when there is penile shortening. Because of the small number of couples and the inclusion of men with an apparently long penis, our results are preliminary, and we welcome replication in a larger sample with a more diverse range of penile lengths. Our results should not be misinterpreted as meaning that increasing penile length will increase sexual pleasure in women.

2.
J Affect Disord ; 289: 1-6, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33906005

RESUMO

The prevalence and risk factors of suicidal ideation in bipolar depression in low- and middle-income countries (LMICs) are poorly understood. This study is a secondary, cross-sectional analysis of a randomized controlled trial from Pakistan, a lower middle-income country. Participants included psychiatric outpatients aged 18 to 65 with a known diagnosis of bipolar disorder and currently in a depressive episode. Suicidality was assessed using the suicide item of the 17-item Hamilton Depression Rating Scale (HAM-D) and levels of severity were categorized as absent, mild/moderate, or severe. Biometric data and biomarkers were obtained. Descriptive statistics were used to describe prevalence and logistic regression applied to establish correlates to suicidal ideation. Among the 266 participants, 67% indicated suicidality of any level and 16% endorsed severe suicidality. Lower body mass index (BMI) (OR = 0.93, 95% CI = 0.88-0.98), higher HAM-D score (OR = 1.29, 95% CI = 1.16-1.43), lower C-reactive protein (CRP) level (OR = 0.53, 95% CI = 0.40-0.70), and increased number of inpatient hospitalizations (OR = 1.16, 95% CI = 1.03-1.31) were identified as significant predictors of suicidality in the fully adjusted regression model. Our findings add to the limited literature on suicidality in bipolar disorder in the LMIC context and suggest roles of biological variables such as BMI and CRP level in predicting suicidal ideation and potentially suicidal behaviours in bipolar depression.

3.
J Clin Med ; 10(4)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669254

RESUMO

BACKGROUND: Optimising treatments for patients with treatment-resistant depression (TRD) is key to reducing the burden of this severe illness. The anti-glucocorticoid medication metyrapone has mixed evidence supporting a role as a possible augmentation treatment in TRD. The degree of treatment resistance in depression has been associated prospectively and retrospectively with elevated inflammation, and inflammatory activity may influence responses to antidepressant treatments. AIMS: To investigate whether levels of pro-inflammatory cytokines are associated with clinical outcomes to metyrapone or placebo. METHODS: A double-blind RCT randomised patients with TRD to 3 weeks of placebo or metyrapone augmentation to ongoing serotonergic antidepressants. No benefit of metyrapone was reported in the primary analysis. The current study assessed levels of pro-inflammatory proteins interleukin-6 (IL-6), tumour necrosis factor (TNFα), c-reactive protein (CRP) and interleukin-10 (IL-10) before randomisation and after treatment as potential moderators and/or mediators of clinical outcomes. RESULTS: The three pro-inflammatory proteins (but not IL-10) were elevated in this sample of patients with TRD compared to a non-affected control group. High pre-treatment IL-6 levels predicted a poorer response in the trial overall but did not moderate response to metyrapone versus placebo. Changes in IL-6 indirectly mediated depression outcome, with metyrapone increasing IL-6 levels and IL-6 increase associated with a poorer outcome on depression. Other inflammatory proteins did not mediate or moderate treatment outcomes. INTERPRETATION: Metyrapone is hypothesised to have a therapeutic effect in depression on the basis of inhibiting the synthesis of cortisol. In this study, metyrapone did not reduce cortisol, possibly due to glucocorticoid system overcompensation). The mediation effect of IL-6 may support this and perhaps help to indicate why the treatment was not effective.

4.
Body Image ; 37: 94-105, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33582531

RESUMO

Body dysmorphic disorder (BDD) and anorexia nervosa (AN) are characterised by body image disturbance. It has been suggested that poor global integration in visual processing may underlie distorted body image, but empirical studies have yielded mixed results. The current study involved two meta-analyses aimed at examining the extent to which poor global processing is evident in BDD and AN. Studies were identified through a systematic literature search up to October 2020. The BDD search yielded 16 studies and the AN search yielded 18 studies. Random-effect models demonstrated a small pooled effect size for BDD (g = -0.44, 95 % CI -0.70, -0.17, p < 0.001) and a moderate pooled effect size for AN (g = -0.63, 95 % CI -0.77, -0.49, p <  .001), with no evidence of significant publication bias for either. The results provide evidence that poor global processing is a transdiagnostic feature of both BDD and AN, although effects may be more pronounced in AN. Our findings highlight the possibility that interventions aimed at promoting global visual processing could prove beneficial in disorders characterised by distorted body image.

5.
BMJ Open ; 10(10): e037198, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33028550

RESUMO

OBJECTIVES: Transcranial magnetic stimulation (TMS) has been used therapeutically for functional (conversion) motor symptoms but there is limited evidence for its efficacy and the optimal protocol. We examined the feasibility of a novel randomised controlled trial (RCT) protocol of TMS to treat functional limb weakness. DESIGN: A double-blind (patient, outcome assessor) two parallel-arm, controlled RCT. SETTING: Specialist neurology and neuropsychiatry services at a large National Health Service Foundation Trust in London, UK. PARTICIPANTS: Patients with a diagnosis of functional limb weakness (Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition). Exclusion criteria included comorbid neurological or major psychiatric disorder, contraindications to TMS or previous TMS treatment. INTERVENTIONS: Patients were randomised to receive either active (single-pulse TMS to primary motor cortex (M1) above resting motor threshold) or inactive treatment (single-pulse TMS to M1 below resting motor threshold). Both groups received two TMS sessions, 4 weeks apart. OUTCOME MEASURES: We assessed recruitment, randomisation and retention rates. The primary outcome was patient-rated symptom change (Clinical Global Impression-Improvement scale, CGI-I). Secondary outcomes included clinician-rated symptom change, psychosocial functioning and disability. Outcomes were assessed at baseline, both TMS visits and at 3-month follow-up. RESULTS: Twenty-two patients were recruited and 21 (96%) were successfully randomised (active=10; inactive=11). Nineteen (91%) patients were included at follow-up (active=9; inactive=10). Completion rates for most outcomes were good (80%-100%). Most patients were satisfied/very satisfied with the trial in both groups, although ratings were higher in the inactive arm (active=60%, inactive=92%). Adverse events were not more common for the active treatment. Treatment effect sizes for patient-rated CGI-I scores were small-moderate (Cliff's delta=-0.1-0.3, CIs-0.79 to 0.28), reflecting a more positive outcome for the active treatment (67% and 44% of active arm-rated symptoms as 'much improved' at session 2 and follow-up, respectively, vs 20% inactive group). Effect sizes for secondary outcomes were variable. CONCLUSIONS: Our protocol is feasible. The findings suggest that supramotor threshold TMS of M1 is safe, acceptable and potentially beneficial as a treatment for functional limb weakness. A larger RCT is warranted. TRIAL REGISTRATION NUMBER: ISRCTN51225587.

6.
Psychol Med ; : 1-10, 2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32713405

RESUMO

BACKGROUND: This trial examined the feasibility, acceptability, and effect sizes of clinical outcomes of an intervention that combines inhibitory control training (ICT) and implementation intentions (if-then planning) to target binge eating and eating disorder psychopathology. METHODS: Seventy-eight adult participants with bulimia nervosa or binge eating disorder were randomly allocated to receive food-specific, or general, ICT and if-then planning for 4 weeks. RESULTS: Recruitment and retention rates at 4 weeks (97.5% and 79.5%, respectively) met the pre-set cut-offs. The pre-set adherence to the intervention was met for the ICT sessions (84.6%), but not for if-then planning (53.4%). Binge eating frequency and eating disorder psychopathology decreased in both intervention groups at post-intervention (4 weeks) and follow-up (8 weeks), with moderate to large effect sizes. There was a tendency for greater reductions in binge eating frequency and eating disorders psychopathology (i.e. larger effect sizes) in the food-specific intervention group. Across both groups, ICT and if-then planning were associated with small-to-moderate reductions in high energy-dense food valuation (post-intervention), food approach (post-intervention and follow-up), anxiety (follow-up), and depression (follow-up). Participants indicated that both interventions were acceptable. CONCLUSIONS: The study findings reveal that combined ICT and if-then planning is associated with reductions in binge eating frequency and eating disorder psychopathology and that the feasibility of ICT is promising, while improvements to if-then planning condition may be needed.

7.
Bipolar Disord ; 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32583630

RESUMO

OBJECTIVES: Cognitive remediation therapy (CRT) may benefit people with bipolar disorder type I and II for whom cognitive impairment is a major contributor to disability. Extensive research has demonstrated CRT to improve cognition and psychosocial functioning in people with different diagnoses, but randomised trials of evidenced therapy programmes are lacking for bipolar disorders. The Cognitive Remediation in Bipolar (CRiB) study aimed to determine whether an established CRT programme is feasible and acceptable for people with bipolar disorders. METHODS: This proof-of-concept, single-blind randomised trial recruited participants aged 18-65 with bipolar disorder, not currently experiencing an episode. They were 1:1 block randomised to treatment-as-usual (TAU) with or without individual CRT for 12 weeks. The partly computerised CRT programme ("CIRCuiTS") was therapist-led and is evidence-based from trials in those with psychotic illnesses. Data were collected and analysed by investigators blinded to group allocation. The main outcomes (week 13 and 25) examined participant retention, intervention feasibility and putative effects of CRT on cognitive and psychosocial functioning via intention-to-treat analyses. TRIAL REGISTRATION: ISRCTN ID32290525. RESULTS: Sixty participants were recruited (02/2016-06/2018) and randomised to CRT (n = 29) or TAU (n = 31). Trial withdrawals were equivalent (CRT n = 2/29; TAU n = 5/31). CRT satisfaction indicated high acceptability. Intention-to-treat analyses (N = 60) demonstrated greater improvements for CRT- than TAU-randomised participants: at both week 13 and 25, CIRCuiTS participants showed larger improvements in the following domains (week 25 effect sizes reported here): IQ (SES = 0.71, 95% CI [0.29,1.13]), working memory (SES = 0.70, 95% CI [0.31,1.10]), executive function (SES = 0.93, 95% CI [0.33,1.54]), psychosocial functioning (SES = 0.49, 95% CI [0.18,0.80]) and goal attainment (SES = 2.02, 95% CI [0.89,3.14]). No serious adverse events were reported. CONCLUSIONS: CRT is feasible for individuals with bipolar disorders and may enhance cognition and functioning. The reported effect sizes from this proof-of-concept trial encourage further investigation in a definitive trial.

8.
Eur Eat Disord Rev ; 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32578311

RESUMO

OBJECTIVE: This systematic review assesses the average duration of untreated eating disorder (DUED) in help-seeking populations at the time of first eating disorder (ED) treatment and investigates the relationship between DUED and symptom severity/clinical outcomes. METHOD: PRISMA guidelines were followed throughout. Selected studies provided information on either: (i) length of DUED, (ii) components of DUED, (iii) cross-sectional associations between DUED and symptom severity, (iv) associations between DUED and clinical outcomes, or (v) experimental manipulation of DUED. Study quality was assessed. RESULTS: Fourteen studies from seven countries were included. Across studies, average DUED weighted by sample size was 29.9 months for anorexia nervosa, 53.0 months for bulimia nervosa and 67.4 months for binge eating disorder. A younger age at time of first treatment was indicative of shorter DUED. Retrospective studies suggest that a shorter DUED may be related to a greater likelihood of remission. Manipulation of DUED by shortening service-related delays may improve clinical outcomes. CONCLUSIONS: Data on length of DUED provide a benchmark for early intervention in EDs. Preliminary evidence suggests DUED may be a modifiable factor influencing outcomes in EDs. To accurately determine the role of DUED, definition and measurement must be uniformly operationalised. Highlights This systematic review is the first to examine duration of untreated eating disorder (DUED) across different eating disorders. Definitions and measurement of DUED and its components vary considerably between studies. Across different eating disorders average DUED weighted by sample size ranges from approximately two and a half years (for anorexia nervosa) to nearly 6 years (for binge eating disorder). DUED appears to be related to age such that younger patients have shorter DUED.

9.
Lancet Psychiatry ; 7(6): 515-527, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32445690

RESUMO

BACKGROUND: Several small studies suggest that the adjunctive use of anti-inflammatory agents might improve depressive symptoms in bipolar disorder. However, there are few well designed, appropriately powered clinical trials assessing the efficacy of these novel treatment strategies. We aimed to assess the efficacy of adjunctive minocycline or celecoxib in this setting. METHODS: This double-blind, 12-week, randomised, placebo-controlled trial was done in four outpatient psychiatric clinics in Pakistan. Eligible participants were adults (aged 18-65 years) with DSM-5 bipolar disorder (type I or II) and a major depressive episode. In a 2 × 2 factorial design, participants were randomly assigned (1:1:1:1) to receive either active minocycline plus active celecoxib, active minocycline plus placebo celecoxib, placebo minocycline plus active celecoxib, or placebo minocycline plus placebo celecoxib. The primary outcome was the mean change from baseline to week 12 in score on the 17-item Hamilton Depression Rating Scale (HAMD-17), assessed in all randomised participants (missing data were imputed and assumed to be missing at random). The trial was registered with ClinicalTrials.gov, NCT02703363. FINDINGS: 266 (17%) of 1542 patients assessed between May 1, 2016, and March 31, 2019, were randomly assigned to receive minocycline plus celecoxib (n=68), minocycline plus placebo (n=66), celecoxib plus placebo (n=66), or placebo plus placebo (n=66). From baseline to week 12, depressive symptoms as per HAMD-17 reduced in all four groups (from 24·5-25·2 to 11·3-12·8), but these reductions did not differ significantly between the groups. In terms of main effects, reductions in HAMD-17 did not differ for patients treated with minocycline (mean adjusted difference vs non-minocycline 1·48 [95% CI -0·41 to 3·36]; p=0·123) or for celecoxib (mean adjusted difference vs non-celecoxib -0·74 [-2·61 to 1·14]; p=0·443). Rates of serious adverse effects did not differ between groups (31 participants had a manic switch, two self-harmed, and one died in a motor vehicle accident). INTERPRETATION: We found no evidence that minocycline or celecoxib was superior to placebo for the treatment of bipolar depression. This large trial casts doubt on the potential therapeutic benefits of adjunctive anti-inflammatory drugs for the acute management of bipolar depression. FUNDING: Stanley Medical Research Institute.


Assuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Transtorno Bipolar/tratamento farmacológico , Celecoxib/uso terapêutico , Minociclina/uso terapêutico , Adulto , Antibacterianos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Celecoxib/administração & dosagem , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minociclina/administração & dosagem , Paquistão/epidemiologia , Placebos/administração & dosagem , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
11.
Sleep Med ; 66: 174-183, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31901759

RESUMO

OBJECTIVE/BACKGROUND: Many patients find cognitive behavioral therapy for insomnia (CBT-I) useful. However, it is currently unknown if those with sub-threshold insomnia also benefit. Here we assessed whether CBT-I is both feasible and acceptable in participants with sub-threshold insomnia. The primary aims were to evaluate participation rates and treatment acceptability, and to establish an effect size for symptom improvement. PATIENTS/METHODS: A total of 199 female participants (Mage 20 ± 5 years) took part. Following baseline assessments, participants were randomly allocated to either a six-week digital CBT-I intervention or a six-week control group receiving puzzles. Additional assessments were performed three-weeks, six-weeks, and six-months later. RESULTS: Participation rates at each survey assessment wave did not differ between the groups (ps > 0.140), though adherence to completing each weekly task was lower in the CBT-I group, p = 0.02. Treatment acceptability was high (M (SD) = 33.61 (4.82), theoretical range 6-42). The CBT-I group showed greater improvement in insomnia symptoms at the end of the intervention compared to the control group (p = 0.013, d = 0.42), with significant variation in outcome (M = 4.69, SD = 5.41). Sub-threshold participants showed a similar pattern of results, whilst those meeting insomnia criteria showed a smaller between-group difference. CBT-I led to improvements in anxiety, paranoia and perceived stress between baseline and end of intervention. Changes in insomnia symptoms were mediated by cognitions about sleep and somatic pre-sleep arousal. CONCLUSIONS: CBT-I provides a benefit even in sub-threshold insomnia. CBT-I may be useful to tackle insomnia symptoms even when they are sub-threshold.

12.
Schizophr Bull ; 46(2): 303-310, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-31150553

RESUMO

Clozapine treatment may have beneficial effects on behavioral outcomes in psychotic disorders, including violent offending. Although clozapine and other antipsychotics have been linked to lower levels of violent behavior, these have been primarily in small selected samples, and population-based estimates have been limited and imprecise. We aimed to assess the effect of clozapine treatment on the rate of violent and nonviolent offending. We carried out a within-person mirror-image study of the Swedish population with linked prescription, hospitalization, and sociodemographic registers. Outcomes were violent, nonviolent, and overall offences occurring before and after clozapine, or olanzapine, initiation. Comparison of effects of clozapine and olanzapine on key variables was modeled with interaction terms. We found periods of mirror-image observation time with clozapine treatment were associated with a much lower rate of violent offending compared to periods before treatment (rate ratio [RR]: 0.13 (95% CI: 0.05, 0.34). Reductions in nonviolent offences were smaller in magnitude (RR: 0.37, 95% CI: 0.17, 0.80). There was a statistically greater rate reduction effect on violent offences for clozapine than olanzapine (RR for interaction: 4.84, 95% CI: 1.56, 14.86, P = .002). In patients with psychotic disorders, clozapine treatment is associated with a lower rate of violent offending compared to olanzapine.

13.
J Affect Disord ; 261: 91-102, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606606

RESUMO

BACKGROUND: Chronotherapy (sleep deprivation, sleep phase shifting and/or the use of bright light) combines non-invasive and non-pharmacological interventions that may act rapidly against depressive symptoms. However, to date no meta-analysis has been conducted to examine their effectiveness. METHODS: We carried out meta-analysis of 16 studies (four randomised controlled trials and 12 open-label case series) with between-subject comparisons between experimental and control conditions for RCTs and within-subject comparisons between baseline and follow-up for all studies. RESULTS: Overall chronotherapy was generally superior to other therapies such as psychotherapy, antidepressants, exercise or light therapy alone after 5-7 days. For RCTs, chronotherapy was favoured (Hedge's g = 0.62, 95% CI 0.23-1.01) compared to control treatments such as antidepressants and exercise. 33.0% of patients were responders after 5-7 days in the chronotherapy group and 1.5% of patients in the control condition (OR = 7.58, 95% CI 2.03-28.28). For the case series, large effect sizes were found by 5-7 days (g = 1.78, 95% CI 1.49-2.07). In the case series, 61.6% of patients were classed as responders. LIMITATIONS: The number of RCTs included in this meta-analysis was small, and the potential for risk of bias could not be ascertained accurately. One specific limitation is that studies nearly all included in-patients and the results may not be generalisable to out-patients, and nearly all the subjects lacked credibility ratings before receiving treatment. CONCLUSIONS: Chronotherapy appears to be effective and well-tolerated in depressed patients. Nevertheless, further clinical and cost effectiveness studies are needed.

14.
Transl Psychiatry ; 9(1): 150, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123309

RESUMO

Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.


Assuntos
Transtornos de Ansiedade/genética , Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/estatística & dados numéricos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/terapia , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Adulto , Criança , Humanos
15.
Int Rev Psychiatry ; 31(4): 367-381, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30950660

RESUMO

The eating disorder clinical and scientific community advocates for the use of a shared approach to healthcare that actively involves patients and carers. A systematic review of the literature on guided self-help or self-help in anorexia nervosa (targeting either the individual affected by the illness or their carers) and meta-analyses of studies using randomised controlled designs for the evaluation of the outcomes: (1) drop-out from end-of-treatment assessment, (2) body mass index (BMI), (3) anxiety, (4) depression and (5) quality of life, were undertaken. Guided self-help was directed to patients in 15 studies and to carers in seven studies. The interventions were based on a variety of theoretical models, used different formats (books and digital materials), and were delivered by individuals with a range of experiences and expertise (e.g. individuals with lived experience of the illness, graduate students, or clinically trained professionals). Guided self-help was associated with significantly lower drop-out from the completion of end-of-treatment assessments compared to a control condition. There was an improvement in carers' wellbeing from skill-sharing interventions. Guided self-help may facilitate patients' treatment engagement and also improve carers' wellbeing.


Assuntos
Anorexia Nervosa/psicologia , Anorexia Nervosa/terapia , Cuidadores , Psicoterapia , Autogestão , Anorexia Nervosa/enfermagem , Humanos
16.
BJPsych Open ; 5(1): e13, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30762508

RESUMO

BACKGROUND: A third of patients diagnosed with major depressive disorder (MDD) experience treatment-resistant depression (TRD). Relatively few pharmacological agents have established efficacy for TRD. Therefore, the evaluation of novel treatments for TRD is a pressing priority. Statins are pleiotropic agents and preclinical studies as well as preliminary clinical trials have suggested that these drugs may have antidepressant properties.AimsTo report on a protocol for a 12-week, randomised, double-blind, placebo-controlled trial of add-on treatment with simvastatin for patients meeting DSM-5 criteria for MDD who have failed to respond to at least two adequate trials with approved antidepressants. The trial has been registered with Clinicaltrials.gov in (ClinicalTrials.gov identifier: NCT03435744). METHOD: After screening and randomisation to the two parallel arms of the trial, 75 patients will receive simvastatin and 75 patients will receive placebo as adjuncts to treatment as usual. The primary outcome is change in Montgomery-Åsberg Depression Rating Scale scores from baseline to week 12 and secondary outcomes include changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. Assessments will take place at screening, baseline, and weeks 2, 4, 8 and 12. Checklists for adverse effects will be undertaken at each visit. Simvastatin (20 mg) will be given once daily. Other secondary outcomes include C-reactive protein and plasma lipids measured at baseline and week 12. RESULTS: This trial will assess simvastatin's efficacy and tolerability as an add-on treatment option for patients with TRD and provide insights into its putative mechanisms of action. CONCLUSIONS: As the first trial investigating the use of simvastatin as an augmentation strategy in patients with TRD, if the results indicate that adjuvant simvastatin is efficacious in reducing depressive symptoms, it will deliver immediate clinical benefit.Declaration of interestI.B.C. and N.H. have given lectures and advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, Astra Zeneca and Janssen pharmaceuticals for which they or their employing institution have been reimbursed. R.R. and M.M.H. have received educational grants and support for academic meetings from Pfizer, Roche, Novartis and Nabiqasim. A.H.Y. has been commissioned to provide lectures and advice to all major pharmaceutical companies with drugs used in affective and related disorders. A.H.Y. has undertaken investigator-initiated studies from Astra Zeneca, Eli Lilly, Lundbeck and Wyeth. None of the companies have a financial interest in this research.

17.
Int Clin Psychopharmacol ; 34(2): 101-107, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30614850

RESUMO

Clozapine is the only evidence-based antipsychotic for treatment-resistant schizophrenia. However, it has considerable side effects, limiting its usability and reducing patients' adherence. One of the most common and distressing side effects is hypersalivation, which can be debilitating, stigmatizing and potentially dangerous through its association with aspiration pneumonia. There is a paucity of evidence guiding possible treatment strategies for hypersalivation. This study aims to examine the efficacy of hyoscine (scopolamine) for clozapine-induced hypersalivation. Fourteen inpatients diagnosed with treatment-resistant schizophrenia, treated with clozapine and suffering from hypersalivation were randomized to receive hyoscine 0.3 mg and placebo daily for 4 weeks each in a randomized, double-blind, placebo-controlled cross-over trial. The primary outcome was improvement in the Toronto Nocturnal Hypersalivation Scale. The secondary outcomes were change in the mass of the pillowcase, anxiety, depression and quality of life. Hypersalivation improved significantly with hyoscine over placebo when measured by the Toronto Nocturnal Hypersalivation Scale (odds ratio=0.21, 95% confidence interval: 0.16-0.28, P<0.001). No significant difference was observed in any of the secondary outcomes. This study showed a beneficial effect of hyoscine over placebo for clozapine-induced hypersalivation.


Assuntos
Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Antagonistas Muscarínicos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Escopolamina/uso terapêutico , Sialorreia/induzido quimicamente , Sialorreia/tratamento farmacológico , Adulto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
J Clin Psychiatry ; 81(1)2019 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-31917904

RESUMO

OBJECTIVE: To perform a systematic review and meta-analysis on research on prevalence and correlates of self-harm in pregnancy and the postpartum year ("perinatal self-harm"). DATA SOURCES: Six databases (EMBASE, MEDLINE, PsycINFO, Maternity and Infant Care Database, CINAHL, Cochrane Controlled Register of Trials) were searched from inception through October 31, 2018. STUDY SELECTION: Inclusion criteria were (1) peer-reviewed articles with (2) data available for estimating prevalence and correlates. Exclusion criteria were (1) studies of women seeking abortion and (2) letters, editorials, or case reports/series. DATA EXTRACTION: Two reviewers independently screened all articles, extracted data, and appraised quality. RESULTS: Of 3,913 articles screened, 39 (reporting 19,191,431 pregnancies) were included. Prevalence ranges were as follows: self-harm during pregnancy (14 studies): 0%-2.39% (median = 0.0004%; interquartile range [IQR], 0.0002%-0.18%); self-harm during postpartum year (10 studies): 0%-2.41% (median = 0.17%; IQR, 0.04%-1.05%); self-harm during pregnancy in women with serious mental illness (SMI) (6 studies): 0%-23.78% (median = 2.16%; IQR, 0.26%-7.9%); self-harm during postpartum year in women with SMI (7 studies): 0%-21.9% (median = 7.97%; IQR, 0%-18%). Key correlates of self-harm during pregnancy and the postpartum year include mental disorder, substance misuse, younger age, being unmarried, and obstetric and neonatal complications. Additionally, a history of self-harm and fetal/infant loss were associated with postpartum self-harm. There were limited data on correlates of perinatal self-harm in women with SMI. CONCLUSIONS: Perinatal self-harm appears to be rare but is associated with adverse obstetric and neonatal outcomes. However, it is common in women with SMI, though there is limited evidence regarding correlates and outcomes in this population. More research into the prevalence, correlates, and outcomes of perinatal self-harm, particularly in women with SMI, is needed.


Assuntos
Período Pós-Parto/psicologia , Complicações na Gravidez/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Feminino , Humanos , Gravidez , Complicações na Gravidez/psicologia , Prevalência , Fatores de Risco , Comportamento Autodestrutivo/etiologia
19.
Int J Stroke ; 14(2): 167-173, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30196790

RESUMO

BACKGROUND AND AIM: Pyrexia-dependent clinical algorithms may under or overdiagnose stroke-associated pneumonia. This study investigates whether inclusion of elevated C-reactive protein as a criterion improves diagnosis. METHODS: The contribution of C-reactive protein ≥30 mg/l as an additional criterion to a Centers for Disease Control and Prevention-based algorithm incorporating pyrexia with chest signs and leukocytosis and/or chest infiltrates to diagnose stroke-associated pneumonia was assessed in 1088 acute stroke patients from 37 UK stroke units. The sensitivity, specificity, and positive predictive value of different approaches were assessed using adjudicated stroke-associated pneumonia as the reference standard. RESULTS: Adding elevated C-reactive protein to all algorithm criteria did not increase diagnostic accuracy compared with the algorithm alone against adjudicated stroke-associated pneumonia (sensitivity 0.74 (95% CI 0.65-0.81) versus 0.72 (95% CI 0.64-0.80), specificity 0.97 (95% CI 0.96-0.98) for both; kappa 0.70 (95% CI 0.63-0.77) for both). In afebrile patients (n = 965), elevated C-reactive protein with chest and laboratory findings had sensitivity of 0.84 (95% CI 0.67-0.93), specificity of 0.99 (95% CI 0.98-1.00), and kappa 0.80 (95% CI 0.70-0.90). The modified algorithm of pyrexia or elevated C-reactive protein and chest signs with infiltrates or leukocytosis had sensitivity of 0.94 (95% CI 0.87-0.97), specificity of 0.96 (95% CI 0.94-0.97), and kappa of 0.88 (95% CI 0.84-0.93) against adjudicated stroke-associated pneumonia. CONCLUSIONS: An algorithm consisting of pyrexia or C-reactive protein ≥30 mg/l, positive chest signs, leukocytosis, and/or chest infiltrates has high accuracy and can be used to standardize stroke-associated pneumonia diagnosis in clinical or research settings. TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN37118456.


Assuntos
Proteína C-Reativa/metabolismo , Pneumonia/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Tomada de Decisão Clínica , Erros de Diagnóstico/prevenção & controle , Feminino , Febre , Humanos , Masculino , Pneumonia/epidemiologia , Sensibilidade e Especificidade , Acidente Vascular Cerebral/epidemiologia , Reino Unido/epidemiologia , Regulação para Cima
20.
J Affect Disord ; 246: 42-51, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30578945

RESUMO

BACKGROUND: Treatment-resistant depression (TRD) contributes substantially to the burden of mood disorders and is undoubtedly an important subpopulation in whom there are clear unmet treatment needs. Despite a paucity of research focusing specifically on TRD, recent studies indicate that inflammatory activity may be particularly elevated in these patients. METHODS: 36 patients with TRD were investigated longitudinally before and after undertaking a specialist inpatient treatment program. 27 inflammatory proteins were compared between patients and a matched sample of non-depressed controls, as well as between treatment responders and non-responders. Treatment outcomes were calculated from depression severity scores before and after admission, and at a long-term follow-up 3-12 months after discharge. RESULTS: TRD patients had higher levels of numerous inflammatory proteins than controls, and elevated interleukins 6 and 8, tumour necrosis factor, c-reactive protein and macrophage inflammatory protein-1 were associated with poorer treatment outcomes. A separate set of proteins (either anti-inflammatory in nature or attenuated at baseline) showed increases during treatment, regardless of clinical response. Participants with the greatest elevations in inflammation tended to be older, more cognitively impaired and more treatment-resistant at baseline. LIMITATIONS: The small sample and large number of comparisons examined in this study must be taken into account when interpreting these results. CONCLUSIONS: However, this study provides empirical support for theories that more severe, chronic or treatment-resistant depressive disorders are associated with dysregulated inflammatory activity. If a predictor or predictors of response in TRD are established, improved and targeted care might be more reliably provided to this vulnerable population.


Assuntos
Citocinas/sangue , Transtorno Depressivo Resistente a Tratamento/sangue , Inflamação/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antidepressivos/uso terapêutico , Biomarcadores/sangue , Estudos de Casos e Controles , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Pesquisa Empírica , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa
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