Psilocybin as a New Approach to Treat Depression and Anxiety in the Context of Life-Threatening Diseases-A Systematic Review and Meta-Analysis of Clinical Trials.2020
Link
Псилоцибин как новый подход к лечению депрессии и тревоги в контексте угрожающих жизни заболеваний - систематический обзор и метаанализ клинических испытаний, 2020 г.
Сгенерированная сводка:
Полученные результаты являются многообещающими и подчеркивают важность исследований трансляции псилоцибина, которые могут привести к клинически значимым исследованиям.
В целом в трех статьях изучались эффекты псилоцибина при лечении депрессии и тревоги, связанных с опасным для жизни заболеванием.
Три включенных исследования были опубликованы между 2011 и 2016 годами, и 92 пациента получали псилоцибин в дозах от 0,2 до 0,4 мг / кг, в зависимости от испытаний.
Соответственно, влияние псилоцибина на BDI или STAI-Trait изучалось отдельно в зависимости от дозы и времени наблюдения после введения псилоцибина.
Оценка систематической ошибки публикации проводилась отдельно с учетом 3 шкал, используемых для измерения эффектов псилоцибина при депрессии через BDI и тревоге через STAI. Графики-воронки указывают на асимметрию в распределении исследований на основе размеров выборки.
Abstract:
Conclusion
This work demonstrated that psilocybin may be effective in reducing symptoms of depression and anxiety. The results also showed the presence of publication bias, which, however, do not invalidate the conclusions of this meta-analysis. The obtained results are promising and emphasize the importance of psilocybin translational research that may lead to clinically relevant studies. Mechanistic studies are also needed to clarify the mechanism of action of the drug.
Result
The detailed steps of the article selection process are depicted as a flow-diagram (,). Initially, the search yielded 722 articles concerning the hypothetical therapeutic use of psilocybin. This initial search included 8 articles obtained through research in other sources. After, duplicates were removed, 670 articles remained and after the screening of titles and abstracts according to PRISMA statement, 32 of them remained and were further evaluated for inclusion and exclusion criteria. Among them, 26 did not meet the inclusion criteria.,Then, seven articles were assessed for eligibility through full-text evaluation and four of them were excluded (Stroud et al., 2018 [,], Lyons and Carhart-Harris, 2018 [,], Carhart-Harris et al., 2017 [,] and Carhart-Harris et al., 2016 [,]), because they were secondary analyses of the same data, and as such none was eligible since a true control group was not present in either of them. Finally, three articles were included in qualitative synthesis and three of them were divided into several effect sizes based on different times of follow-up after psilocybin administration. In a general view, the three articles studied the effects of psilocybin in the treatment of depression and anxiety associated with a life-threatening disease. The data from Ross et al., 2016 [,] was divided in seven data groups and the data from Griffiths et al., 2016 [,] and from Grob et al., 2011 [,] were divided into two data groups each, considering different times of follow-up after psilocybin administration. In total, 11 effect sizes were included in this meta-analysis.,The main characteristics of the included trials are outlined in ,. The three included studies were published between 2011 and 2016 and 92 patients received psilocybin with doses ranging from 0.2 to 0.4 mg/kg, depending on the trials. The different units used to measure doses (some of them depending on the weight of the patients) made results standardization difficult. Patients had depression and anxiety associated with life-threatening diseases, namely aggressive oncologic conditions. Although psilocybin is a natural substance found in some mushrooms, it was synthesized (in the laboratory) for the trials and was administered in the form of oral capsules. Concerning the duration of the intervention, results were usually assessed through the scales, days after the administration of psilocybin and in a longer follow-up, in some cases up to three months.,The results found in the assessment of the risk of publication bias from the included studies are summarized in ,. In general, all the studies satisfied the seven domains of bias defined by Cochrane Collaboration. All the included articles had a focused issue and all the patients who entered the trial were properly accounted for at its conclusion. Aside from the experimental intervention, both the control and intervention groups were treated equally, and all clinically important outcomes were considered. The randomization process was applied in the three articles that were also double-blinded.,BDI and STAI were considered the psychometric scales for this work since they are the most widely used in clinical settings to quantify symptoms of either depression or anxiety.,The meta-analysis results for the effects of psilocybin in depression through BDI are graphically reported in ,A and ,. For BDI, 11 effect sizes were considered, including 92 patients, with a diagnosis of depression and anxiety associated with a life-threatening disease. It was concluded that the intervention group was significantly favored when compared to the control group (WMD = −4.589; 95% CI = −4.207 to −0.971; ,-value = 0.002). For these results, a fixed effects model was used, given the homogeneity of the studies (I, = 0%).,The meta-analysis results for the effects of psilocybin in anxiety through STAI-Trait and STAI-State are graphically reported in ,B,C, respectively and ,.,For STAI-Trait, 11 effect sizes were considered, including 92 patients, with a diagnosis of depression and anxiety associated with a life-threatening disease. Among these, 28 patients had genitourinary cancer, 26 had breast cancer, 16 had digestive cancer, 12 had hematologic malignancies and 10 had other oncologic pathologies. All patients were in advanced stages of their illnesses and some had recurrent metastatic diseases. Apart from that, all patients had also been diagnosed using the DSM V meeting criteria for either chronic adjustment disorder with anxiety, chronic adjustment disorder with mixed anxiety and depressed mood, dysthymic disorder, GAD, MDD or dual diagnosis between GAD and MDD or GAD and dysthymic disorder.,It was concluded that the intervention group was significantly favored when compared to the control group (WMD = −5.906; 95% CI = −7.852 to −3.960; ,-value ˂ 0.001). For these results, a fixed effects model was used, given the homogeneity between studies (I, = 0%).,For STAI-State, 9 effect sizes were considered, including 41 patients, with a diagnosis of depression and anxiety associated with a life-threatening disease (oncologic conditions). For this outcome, it was concluded that the intervention group was significantly favored when compared to the control group (WMD = −6.032; 95% CI = −8.900 to −3.164; ,-value ˂ 0.001). For these results, a fixed effects model was used, given the homogeneity between studies (I, = 0%).,A subgroup analysis was performed for each primary outcome of the study, except for STAI-State because of the limited number of studies reporting this outcome (,). Accordingly, the influence of psilocybin in either BDI or STAI-Trait was studied separately depending on the dose and on the follow-up time after psilocybin administration.,It was shown that psilocybin induces reduction in both BDI and STAI-Trait at all the tested doses, but the reduction is not dose-dependent. In fact, compared to the control group, this outcome was only statistically significant at the doses of 0.4 mg/kg for BDI and of 0.3 and 0.4 mg/kg for STAI-Trait.,Concerning the time of the follow-up, psilocybin induces statistically significant results in a period of 38 to 189 days in BDI and in 14 to 189 days in STAI-Trait.,The sensitivity analysis was performed by excluding some studies and evaluating how those studies would affect the results (results not shown). This analysis indicates that the pooled effects of psilocybin in depression and anxiety through BDI, STAI-Trait and STAI-State did not change substantially if a few studies were omitted. The sensitivity analysis proved that the overall results obtained in this meta-analysis are robust.,Publication bias was examined through funnel plots and statistically using the Trim and Fill method (results not shown). Publication bias evaluation was performed separately considering the 3 scales used to measure the effects of psilocybin in depression, through BDI and anxiety, through STAI. Funnel plots indicate asymmetries in the distribution of studies based on sample sizes. The presence of publication bias was further explored using Egger’s regression test. This test indicates evidence of publication bias for the effects of psilocybin on depression and anxiety (,-value > 0.05).,Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were evaluated in this meta-analysis as secondary outcomes. The obtained results are summarized in ,. As noted, psilocybin produced significant increases in SBP and DBP, up to 6 (,-value < 0.017) and 5 h (,-value < 0.001) following administration, respectively. The DBP verified increases between 1.194 and 11.381 mmHg, being the average of the increase 7.741 mmHg. Both SBD and DBP tended to stabilize to normal values after 6 or more hours after administration. Psilocybin also significantly increases the heart rate, this increase being highest on the 3rd and 4th hours following administration. Similarly to what was verified for SBP and DBP, heart rate tended to stabilize after 6 or more hours after the administration.