目的:虽然经常使用,比较青少年5-羟色胺/多巴胺拮抗剂/部分激动剂(SDAs)催乳素水平和性不良反应(SeAEs)的前瞻性数据很少.
方法:4-17岁青年,首次使用SDA(≤1周暴露)或无SDA≥4周随访≤12周临床医师选择阿立哌唑,奥氮平,喹硫平或利培酮。血清催乳素水平,每月评估SDA血浆水平和基于评分量表的SeAE。
结果:总之,396名青年(年龄=14.0±3.1岁,男性参与者=55.1%,情绪谱系障碍=56.3%,精神分裂症谱系障碍=24.0%,攻击性行为障碍=19.7%;SDA-Naive=77.8%)随访10.6±3.5周。峰值催乳素水平/任何高催乳素血症/三重正常上限催乳素水平在利培酮中最高(中位数=56.1ng/mL/发生率=93.5%/44.5%),其次是奥氮平(中位数=31.4ng/mL/发生率=42.7/76.4%/7.3%),喹硫平(中位数=19.5ng/mL/发生率=39.7%/2.5%)和阿立哌唑(中位数=7.1ng/mL/发生率=5.8%/0.0%)(均p<0.0001),利培酮和奥氮平在4-5周时达到峰值水平。总之,26.8%有≥1例新发SeAE(利培酮=29.4%,喹硫平=29.0%,奥氮平=25.5%,阿立哌唑=22.1%,p=0.59)。最常见的SeAE是月经紊乱=28.0%(利培酮=35.4%,奥氮平=26.7%,喹硫平=24.4%阿立哌唑=23.9%,p=0.58),勃起减少=14.8%(奥氮平=18.5%,利培酮=16.1%,喹硫平=13.6%,阿立哌唑=10.8%,p=0.91)和性欲下降=8.6%(利培酮=12.5%,奥氮平=11.9%,喹硫平=7.9%,阿立哌唑=2.4%,p=0.082),最不常见的是男性乳房发育症=7.8%(喹硫平=9.7%,利培酮=9.2%,阿立哌唑=7.8%,奥氮平=2.6%,p=0.61),溢乳=6.7%(利培酮=18.8%,喹硫平=2.4%,奥氮平=0.0%,阿立哌唑=0.0%,p=0.0008)和乳腺痛=5.8%(奥氮平=7.3%,利培酮=6.4%,阿立哌唑=5.7%,喹硫平=3.9%,p=0.84)。青春期后状态和女性与催乳素水平和SeAE显着相关。血清催乳素水平很少与SeAE相关(占所有分析关联的16.7%),除了严重的高泌乳素血症与性欲下降(p=0.013)和勃起功能障碍(p=0.037)在第4周之间的关系,并且在第4周有溢乳(p=0.0040),第12周(p=0.013)和最后一次访问(p<0.001)。
结论:利培酮,其次是奥氮平,与最大的催乳素升高有关,喹硫平几乎没有催乳素升高作用,尤其是,阿立哌唑.除了利培酮相关的溢乳,SeAE在各个SDA之间没有显着差异,只有溢乳,性欲下降和勃起功能障碍与催乳素水平相关。在青年时期,SeAE不是显著升高的催乳素水平的敏感标志物。
Although these agents are used frequently, prospective data comparing serotonin/dopamine antagonists/partial agonists (SDAs) in youth regarding prolactin levels and sexual adverse effects (SeAEs) are scarce.
Youth aged 4 to 17 years, SDA-naive (≤1 week exposure) or SDA-free for ≥4 weeks were followed for ≤12 weeks on clinician\'s-choice aripiprazole, olanzapine, quetiapine, or risperidone. Serum prolactin levels, SDA plasma levels, and rating scale-based SeAEs were assessed monthly.
Altogether, 396 youth (aged 14.0 ± 3.1 years, male participants = 55.1%, mood spectrum disorders = 56.3%, schizophrenia spectrum disorders = 24.0%, aggressive-behavior disorders = 19.7%; SDA-naive = 77.8%) were followed for 10.6 ± 3.5 weeks. Peak prolactin levels/any hyperprolactinemia/triple-upper-limit-of-normal-prolactin level were highest with risperidone (median = 56.1 ng/mL/incidence = 93.5%/44.5%), followed by olanzapine (median = 31.4 ng/mL/incidence = 42.7/76.4%/7.3%), quetiapine (median = 19.5 ng/mL/incidence = 39.7%/2.5%) and aripiprazole (median = 7.1 ng/mL/incidence = 5.8%/0.0%) (all p < .0001), with peak levels at 4 to 5 weeks for risperidone and olanzapine. Altogether, 26.8% had ≥1 newly incident SeAEs (risperidone = 29.4%, quetiapine = 29.0%, olanzapine = 25.5%, aripiprazole = 22.1%, p = .59). The most common SeAEs were menstrual disturbance = 28.0% (risperidone = 35.4%, olanzapine = 26.7%, quetiapine = 24.4% aripiprazole = 23.9%, p = .58), decreased erections = 14.8% (olanzapine = 18.5%, risperidone = 16.1%, quetiapine = 13.6%, aripiprazole = 10.8%, p = .91) and decreased libido = 8.6% (risperidone = 12.5%, olanzapine = 11.9%, quetiapine = 7.9%, aripiprazole = 2.4%, p = .082), with the least frequent being gynecomastia = 7.8% (quetiapine = 9.7%, risperidone = 9.2%, aripiprazole = 7.8%, olanzapine = 2.6%, p = 0.61),
galactorrhea = 6.7% (risperidone = 18.8%, quetiapine = 2.4%, olanzapine = 0.0%, aripiprazole = 0.0%, p = .0008), and mastalgia = 5.8% (olanzapine = 7.3%, risperidone = 6.4%, aripiprazole = 5.7%, quetiapine = 3.9%, p = .84). Postpubertal status and female sex were significantly associated with prolactin levels and SeAEs. Serum prolactin levels were rarely associated with SeAEs (16.7% of all analyzed associations), except for the relationship between severe hyperprolactinemia and decreased libido (p = .013) and erectile dysfunction (p = .037) at week 4, and with
galactorrhea at week 4 (p = .0040), week 12 (p = .013), and last visit (p < .001).
Risperidone, followed by olanzapine, was associated with the largest prolactin elevations, with little prolactin-elevating effects of quetiapine and, especially, aripiprazole. Except for risperidone-related
galactorrhea, SeAEs did not differ significantly across SDAs, and only
galactorrhea, decreased libido, and erectile dysfunction were associated with prolactin levels. In youth, SeAEs are not sensitive markers for significantly elevated prolactin levels.