The effect of ketamine on psychopathology and implications for understanding schizophrenia and its therapeutic use: a meta-analysis
The effect of ketamine on psychopathology and implications for understanding schizophrenia and its therapeutic use: a meta-analysis
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DOI：
10.1192/bjo.2021.634
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发表时间：
2021-06-18
期刊：
影响因子：
5.4
通讯作者：
Howes O
中科院分区：
文献类型：
--
作者：
Beck K;Hindley G;Borgan F;Ginestet C;McCutcheon R;Brugger S;Driesen N;Ranganathan M;D'Souza D;Taylor M;Krystal J;Howes O
对氯胺酮对健康志愿者和精神分裂症患者精神病理学的影响及其影响因素进行荟萃分析。氯胺酮越来越多地用于治疗抑郁症和其他精神疾病，但可能会引起类似精神分裂症的症状。尽管如此，氯胺酮引起的症状的一致性和程度，或者影响氯胺酮对这些症状的影响的因素仍然未知。在MEDLINE、EMBASE和PsychINFO数据库中检索了使用简明精神病评定量表（BPRS）或阳性和阴性综合征量表（PANSS）报告健康受试者或精神分裂症患者急性氯胺酮激发后症状的受试者内安慰剂对照研究。两名独立的研究者提取了研究水平的数据进行随机效应荟萃分析。提取BPRS和PANSS总分、阳性和阴性评分。进行亚组分析，检查以下因素的影响：设盲状态、氯胺酮制剂、输注方法和氯胺酮与安慰剂之间的时间。标准化的平均变化分数被用作个体研究的效应量。计算氯胺酮和安慰剂之间总BPRS、阳性和阴性BPRS和PANSS的标准化平均变化。在检索到的7819篇引文中，纳入了36项涉及健康受试者的研究。总体样本包括725名接触氯胺酮和安慰剂的健康志愿者。氯胺酮在健康受试者中诱导了短暂精神病理学的显著增加，标准化平均变化（SMC）= 1.50（95% CI = 1.23至1.77），p <0.0001），阳性（SMC = 1.55（95%CI = 1.29至1.81），p <0.0001）和阴性（SMC = 1.16，（95%CI = 0.96至1.35），p <0.0001）症状评级。阳性症状的这种影响显著大于阴性症状（p = 0.004）。相对于单独输注，推注后持续输注增加了氯胺酮对阳性症状的影响（p = 0.006）。单日研究设计增加了氯胺酮对总症状的影响（p = 0.007），但年龄和性别没有调节作用。精神分裂症研究的荟萃分析研究不足。在这些研究中，两项研究发现氯胺酮给药后症状显著增加，总症状和阳性症状显著增加。只有一项研究发现氯胺酮的阴性症状严重程度增加。这些发现表明，急性氯胺酮给药诱导精神分裂症样精神病，具有较大的效应量，但阳性症状的增加大于阴性症状，并且当使用推注时。这些发现表明，在其治疗用途中应避免大剂量，以尽量减少诱导一过性阳性精神病症状的风险。
To conduct a meta-analysis of the effect of ketamine on psychopathology in healthy volunteers and patients with schizophrenia, and the experimental factors affecting this. Ketamine is increasingly used to treat depression and other psychiatric disorders but can induce schizophrenia-like symptoms. Despite this, the consistency and magnitude of symptoms induced by ketamine, or what factors influence the effects of ketamine on these remain unknown. MEDLINE, EMBASE and PsychINFO databases were searched for within-subject placebo controlled studies reporting symptoms using the Brief Psychiatric Rating Scale (BPRS) or Positive and Negative Syndrome Scale (PANSS) in response to an acute ketamine challenge in healthy participants or people with schizophrenia. Two independent investigators extracted study-level data for a random-effects meta-analysis. Total, positive and negative BPRS and PANSS scores were extracted. Sub-group analyses were conducted examining the effect of: blinding status, ketamine preparation, infusion method and time between ketamine and placebo condition. Standardized mean change scores were used as effect sizes for individual studies. Standardized mean changes between ketamine and placebo for total, positive and negative BPRS and PANSS were calculated. Of 7819 citations retrieved, 36 studies involving healthy participants were included. The overall sample included 725 healthy volunteers exposed to both the ketamine and placebo condition. Ketamine induced a significant increase in transient psychopathology in healthy participants, for total (Standardized mean change (SMC) = 1.50 (95% CI = 1.23 to 1.77), p < 0.0001), positive (SMC = 1.55 (95% CI = 1.29 to 1.81), p < 0.0001) and negative (SMC = 1.16, (95% CI = 0.96 to 1.35), p < 0.0001) symptom ratings, relative to the placebo condition. This effect was significantly greater for positive symptoms than negative symptoms (p = 0.004). Bolus followed by constant infusion increased ketamine's effect on positive symptoms relative to infusion alone (p = 0.006). Single-day study design increased ketamine's effect on total symptoms (p = 0.007), but age and gender did not moderate effects. There were insufficient studies for meta-analysis of studies in schizophrenia. Of these studies, two found a significant increase in symptoms with ketamine administration in total and positive symptoms. Only one study found an increase in negative symptom severity with ketamine. These findings show that acute ketamine administration induces schizophrenia-like symptomatology with large effect sizes but there is a greater increase in positive than negative symptoms, and when a bolus is used. These findings suggest bolus doses should be avoided in its therapeutic use to minimize the risk of inducing transient positive psychotic symptoms.