Child Study Center, Yale School of Medicine, New Haven, Connecticut, USA.
Department of Psychiatry and Yale School of Medicine, New Haven, Connecticut, USA.
J Child Adolesc Psychopharmacol. 2023 Feb;33(1):20-26. doi: 10.1089/cap.2022.0086.
Ketamine has proven effective as a rapid-acting antidepressant agent. Several adult studies have investigated the association between ketamine's acute dissociative effects and depression response, but no studies have examined the association in adolescents with treatment-resistant depression (TRD). We conducted a secondary data analysis of 16 adolescent participants who participated in a randomized, single-dose, midazolam-controlled crossover trial of ketamine in adolescents with depression. We examined the association between the acute dissociative symptoms (measured at 60 minutes following start of infusion using the Clinician-Administered Dissociative States Scale [CADSS], and its three subscales: depersonalization, derealization, amnesia) and response and depression symptom improvement at 1'day (using the Montgomery-Åsberg Depression Rating Scale). Within the ketamine group, there were no significant associations between dissociation symptoms or CADSS subscale scores and magnitude of depression symptom improvement or likelihood of ketamine response. When receiving midazolam, there was no significant association between overall dissociation symptoms and magnitude or likelihood of response of depressive symptoms. Higher levels of symptoms on the 'depersonalization' CADSS subscale when receiving midazolam were associated with less improvement in depression symptoms at 1 day following infusion. In contrast to some adult literature, the current data do not show a relationship between acute dissociative effects and antidepressant response to ketamine in pediatric patients with TRD. Interpretation may be limited by the small sample size, reducing the power to detect small or medium associations. Future research should utilize larger samples to more definitively measure the magnitude of association between acute dissociative symptoms and later antidepressant response to ketamine and to assess the relationship to trial design (e.g., crossover vs. parallel trial, comparison condition utilized and number of infusions) within both adult and pediatric populations. NCT02579928.
氯胺酮已被证明是一种有效的快速抗抑郁药。几项成人研究调查了氯胺酮的急性分离效应与抑郁反应之间的关系，但没有研究在青少年治疗抵抗性抑郁症（TRD）中检查这种关系。我们对 16 名参加了一项关于氯胺酮治疗青少年抑郁症的随机、单剂量、咪达唑仑对照交叉试验的青少年参与者进行了二次数据分析。我们研究了急性分离症状（在输注开始后 60 分钟使用临床医生管理的分离状态量表[CADSS]及其三个子量表：人格解体、现实解体、遗忘）与反应之间的关系和抑郁症状改善在 1 天（使用蒙哥马利-Åsberg 抑郁评定量表）。在氯胺酮组中，分离症状或 CADSS 子量表评分与抑郁症状改善的程度或氯胺酮反应的可能性之间没有显著关联。在接受咪达唑仑时，总体分离症状与抑郁症状改善的程度或反应的可能性之间没有显著关联。接受咪达唑仑时，CADSS 子量表上“人格解体”症状水平较高与输注后 1 天抑郁症状改善较少相关。与一些成人文献相比，目前的数据并没有显示在 TRD 儿科患者中，急性分离效应与氯胺酮抗抑郁反应之间存在关系。解释可能受到小样本量的限制，降低了检测小或中等关联的能力。未来的研究应该利用更大的样本量，更明确地测量急性分离症状与氯胺酮治疗后抗抑郁反应之间的关联程度，并评估与试验设计（例如，交叉与平行试验、比较条件的使用和输注次数）的关系，在成人和儿科人群中。NCT02579928。
