Insomnia and somnolence associated with second-generation antidepressants during the treatment of major depression: a meta-analysis.

BACKGROUND: Sleep reduction or enhancement is frequently observed with second-generation antidepressant treatments, and they can be beneficial or harmful depending on the symptom profile of each subject. Nevertheless, relatively little attention has been given so far to rank those effects across compounds. The aim of this meta-analysis is to provide quantitative data about short-term rates of insomnia and somnolence associated with 14 second-generation antidepressants during the treatment of major depression. METHODS: A literature search and a search of unpublished documents were performed. Eligible studies focusing on MD patients treated with second-generation antidepressants were entered in the analysis. Our primary outcome measures were insomnia and somnolence rates induced by antidepressants as compared with those associated with placebo. Sensitivity analyses were carried out as well. RESULTS: Ten second-generation antidepressants showed higher rates of insomnia than placebo. The highest incidence was found for bupropion and desvenlafaxine. Agomelatine was the only antidepressant with a lower likelihood of inducing insomnia than placebo. Eleven antidepressants were associated with higher rates of somnolence than placebo. Fluvoxamine and mirtazapine showed the highest frequency of somnolence. Bupropion induced somnolence to a lower extent than placebo. Sensitivity analyses showed a degree of variation of those findings. DISCUSSION: Antidepressants are associated with different insomnia and somnolence rates, mainly depending on their mechanisms of action. Despite some limitations, we underscore that the treatment-emergent insomnia and/or somnolence are frequent, and they could be used in clinical practice to face the specific needs of each patient.

Antipsychotic response in the first week predicts later efficacy.

BACKGROUND AND AIMS: Time of onset of antipsychotic action is still a debated matter. We aimed to replicate and extend previous findings that early response can predict subsequent non-response. METHODS: 86 acutely psychotic patients treated with haloperidol were studied. RESULTS: A PANSS reduction ≤16% at 1 week predicts non-response at 3 weeks of treatment (specificity 92%, sensitivity 82%). Conversely, a PANSS reduction ≥23% at 1 week of treatment predicts response at 3 weeks, with a specificity of 84% and a sensitivity of 86%. CONCLUSION: Our results confirm that an early response to antipsychotic treatment accurately predicts the treatment effectiveness and extends it to a prediction performed as early as 1 week.

Case-control association study for 10 genes in patients with schizophrenia: influence of 5HTR1A variation rs10042486 on schizophrenia and response to antipsychotics.

The aim of this study is to investigate possible associations between a set of single-nucleotide polymorphisms (SNPs) within 10 genes with Schizophrenia (SCZ) and response to antipsychotics in Korean in-patients treated with antipsychotics. Two hundred and twenty-one SCZ in-patients and 170 psychiatrically healthy controls were genotyped for 42 SNPs within ABCB1, ABCB4, TAP2, CLOCK, CPLX1, CPLX2, SYN2, NRG1, 5HTR1A and GPRIN2. Baseline and final clinical measures, including the Positive and Negative Symptoms Scale (PANSS), were recorded. Rs10042486 within 5HTR1A was associated with both SCZ and clinical improvement on PANSS total scores as well as on PANSS positive and PANSS negative scores. The haplotype analyses focusing on the four, three and two blocks' haplotypes within 5HTR1A confirmed such findings as well. We did not observe any significant association between the remaining genetic variants under investigation in this study and clinical outcomes. Our preliminary findings suggest that rs10042486 within 5HTR1A promoter region could be associated with SCZ and with clinical improvement on PANSS total, positive and negative scores in Korean patients with SCZ. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions.

Changes in attitude towards LAI antipsychotic maintenance treatment: A two-year follow-up study.

BACKGROUND: To present real-world evidence on the effects of switching from oral to long-acting injectable (LAI) antipsychotic maintenance treatment (AMT) in a sample of clinically stable patients with schizophrenia, with regard to subjective experience of treatment, attitude towards drug and quality of life. METHODS: 50 clinically stable adult schizophrenic outpatients were recruited. At the time of enrolment (T0), all patients were under a stabilized therapy with a single oral second-generation antipsychotic (SGA) and were switched to the equivalent maintenance regimen with the long-acting formulation of the same antipsychotic. 43 patients completed the 24-month prospective, longitudinal, open-label, observational study. Participants were assessed at baseline (T0), after 12 (T1) and 24 months (T2), using psychometric scales (PANSS, YMRS and MDRS) and patient-reported outcome measures (SWN-K, DAI-10 and SF-36). RESULTS: The switch to LAI-AMT was associated with a significant clinical improvement at T1 and T2 compared to baseline (T0). All of the psychometric indexes, as well as patients' subjective experience of treatment (SWN-K), and quality of life (SF-36) showed a significant improvement after one year of LAI-AMT, with stable results after two years. Patients' attitude towards drug (DAI-10) increased throughout the follow-up period, with a further improvement during the second year. CONCLUSIONS: The switch to LAI-AMT may help to address the subjective core of an optimal recovery in stabilized schizophrenic patients. A sustained improvement in patients' attitude towards drug may help to achieve patient's compliance. The size of this study needs to be expanded to produce more solid and generalizable results.

Mindfulness-based cognitive therapy vs. psycho-education for patients with major depression who did not achieve remission following antidepressant treatment.

Mindfulness-based cognitive therapy (MBCT) showed efficacy for currently depressed patients. However, most of the available studies suffer from important methodological shortcomings, including the lack of adequate control groups. The present study aims to compare MBCT with a psycho-educational control group designed to be structurally equivalent to the MBCT program but excluding the main putative "active ingredient" of MBCT (i.e., mindfulness meditation practice) for the treatment of patients with major depression (MD) who did not achieve remission following at least 8 weeks of antidepressant treatment. Out of 106 screened subjects, 43 were randomized to receive MBCT or psycho-education and were prospectively followed for 26 weeks. MD severity was assessed with the Hamilton Rating Scale for Depression (HAM-D) and the Beck Depression Inventory-II (BDI-II). Measures of anxiety, mindfulness, and quality of life were also included. All assessments were performed at baseline, 4, 8, 17 and 26-weeks. Both HAM-D and BDI scores, as well as quality of life and mindfulness scores, showed higher improvements, which were particularly evident over the long-term period, in the MBCT group than in the psycho-education group. Although limited by a small sample size, the results of this study suggest the superiority of MBCT over psycho-education for non-remitted MD subjects.

Newer antidepressants and panic disorder: a meta-analysis.

Selective serotonin reuptake inhibitors and venlafaxine are currently considered as first-line agents for patients with panic disorder (PD). However, a systematic comparison of newer antidepressants for the treatment of PD is lacking thus far. Eligible studies focusing on PD patients treated with newer antidepressants were entered in the Cochrane Collaboration Review Manager. Our primary outcome measure was the mean change in panic symptoms from the baseline to the endpoint in patients treated with antidepressants as compared with those treated with placebo. Secondary outcome measures included the mean change in the overall anxiety scores and dropout rates. Sensitivity analyses were also carried out. Fifty studies focusing on 5236 patients were included. The following antidepressants were significantly superior to placebo for PD patients with the following increasing order of effectiveness: citalopram, sertraline, paroxetine, fluoxetine, and venlafaxine for panic symptoms and paroxetine, fluoxetine, fluvoxamine, citalopram, venlafaxine, and mirtazapine for overall anxiety symptoms. Aside from reboxetine and fluvoxamine, all drugs were associated with significantly lower dropout rates as compared with placebo. Several clinical variables moderated clinical outcomes. However, because of some inconsistencies across the studies and limited evidence for some drugs under investigation, further head-to-head comparisons are required.

Case-control association study of 36 single-nucleotide polymorphisms within 10 candidate genes for major depression and bipolar disorder.

In this study we investigated 36 single nucleotide polymorphisms within 10 genes previously associated with major depression and bipolar disorder, as well as with the response to their treatment (ABCB1, ABCB4, TAP2, CLOCK, CPLX1, CPLX2, SYN2, NRG1, 5HTR1A and GPRIN2). No association with mood disorders and clinical outcomes was observed.

Possible influence of CREB1, CREBBP and CREM variants on diagnosis and treatment outcome in patients with schizophrenia.

The present study explores whether some single nucleotide polymorphisms (SNPs) within CREB1 (rs2709377 and rs6740584), CREBBP (rs2239317, rs2239316, rs3025702, rs130021, rs130005, rs129974 and rs9392) and CREM (rs1148247, rs4934735, rs12775799, rs6481941 and rs16935888) could be associated with schizophrenia (SKZ) and whether they could predict clinical outcomes in Korean in-patients treated with antipsychotics. Two-hundred twenty one in-patients suffering from SKZ and 170 psychiatrically healthy controls were genotyped for 10 SNPs within CREB1, CREBBP and CREM. All patients were assessed for the severity of illness at baseline and at discharge by means of the Positive and Negative Symptoms Scale (PANSS). Our findings suggest the lack of influence of SNPs under investigation in the present study on the susceptibility to SKZ and on the response to antipsychotics. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions.

Case-control association study of 14 variants of CREB1, CREBBP and CREM on diagnosis and treatment outcome in major depressive disorder and bipolar disorder.

Some evidence suggests an association between genetic variants within the cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), CREB binding protein (CREBBP) and cAMP response element-modulator (CREM) and several psychiatric disorders. The present study investigated whether some single nucleotide polymorphisms (SNPs) within these genes could be associated with major depressive disorder (MDD) and bipolar disorder (BD) and whether they could predict clinical outcomes in Korean in-patients treated with antidepressants and mood stabilizers, respectively. The sample comprised 145 patients with MDD, 132 patients with BD and 170 psychiatrically healthy controls. Participants were genotyped for 14 SNPs within CREB1, CREBBP and CREM. Baseline and final clinical measures, including the Montgomery-Åsberg Depression Rating Scale and Young Mania Rating Scale for patients with MDD and BD, respectively, were recorded. All p-values were 2-tailed, and statistical significance was conservatively set at the 0.006 level in order to reduce the likelihood of false positive results. We failed to observe any association of the 14 SNPs genotypes or alleles with clinical improvement, response and remission rates as well as final outcomes in any of such disorders. Our findings suggest that the 14 SNP under investigation in our study do not influence diagnosis and treatment response in patients with MDD and BD. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions.

Controlling access to suicide means.

BACKGROUND: Restricting access to common means of suicide, such as firearms, toxic gas, pesticides and other, has been shown to be effective in reducing rates of death in suicide. In the present review we aimed to summarize the empirical and clinical literature on controlling the access to means of suicide. METHODS: This review made use of both MEDLINE, ISI Web of Science and the Cochrane library databases, identifying all English articles with the keywords "suicide means", "suicide method", "suicide prediction" or "suicide prevention" and other relevant keywords. RESULTS: A number of factors may influence an individual's decision regarding method in a suicide act, but there is substantial support that easy access influences the choice of method. In many countries, restrictions of access to common means of suicide has lead to lower overall suicide rates, particularly regarding suicide by firearms in USA, detoxification of domestic and motor vehicle gas in England and other countries, toxic pesticides in rural areas, barriers at jumping sites and hanging, by introducing "safe rooms" in prisons and hospitals. Moreover, decline in prescription of barbiturates and tricyclic antidepressants (TCAs), as well as limitation of drugs pack size for paracetamol and salicylate has reduced suicides by overdose, while increased prescription of SSRIs seems to have lowered suicidal rates. CONCLUSIONS: Restriction to means of suicide may be particularly effective in contexts where the method is popular, highly lethal, widely available, and/or not easily substituted by other similar methods. However, since there is some risk of means substitution, restriction of access should be implemented in conjunction with other suicide prevention strategies.