Räsänen P, Hakko H, Tiihonen J
Department of Psychiatry, University of Oulu, Finland.
J Clin Psychopharmacol. 1999 Aug;19(4):297-302. doi: 10.1097/00004714-199908000-00002.
The role of serotonin autoreceptor antagonism in major depression has been a matter of intense debate in recent years. On the basis of animal experiments, it has been suggested that the blockade of this autoreceptor with pindolol during concomitant treatment with selective serotonin reuptake inhibitors (SSRIs) would result in a rapid and augmented antidepressant effect, but it has also been argued that the possible augmenting effect of pindolol is due to the beta-blocking properties of this drug. Results from the first human studies have also been controversial. We used a national computer-based central register to study the cumulative incidence of the use of beta-adrenergic receptor antagonists and antidepressant drugs, as well as the point prevalence of disability pensions as a result of major affective disorders (296, DSM-III-R; F30-F34, ICD-10) at the end of a 3-year follow-up period. Our results from a very large database (total N = 30,485) indicate that the use of pindolol is associated with a marked reduction (from 29% to 52%) in the prevalence of disability pensions resulting from major affective disorders when compared with the use of other beta-adrenergic receptor antagonists. The use of pindolol was associated with a slightly lower rate of antidepressant use when compared with other beta-adrenergic receptor antagonists and especially when compared with propranolol. The results suggest that long-term therapy with pindolol treatment augments the pharmacologic effect of antidepressant drugs (especially SSRIs) among patients with major affective disorders. The finding that patients receiving pindolol have a lower prevalence of disability pensions resulting from major affective disorders indicates that the prevalence of severe treatment-resistant major affective disorders could be decreased markedly by using pindolol as the first-choice beta-adrenergic receptor antagonist in the treatment of cardiovascular diseases whenever possible among those patients who have experienced at least one depressive episode and are receiving antidepressant treatment.
近年来，5-羟色胺自身受体拮抗作用在重度抑郁症中的作用一直是激烈争论的焦点。基于动物实验，有人提出在与选择性5-羟色胺再摄取抑制剂（SSRI）联合治疗期间用吲哚洛尔阻断这种自身受体将产生快速且增强的抗抑郁作用，但也有人认为吲哚洛尔的可能增强作用归因于该药物的β受体阻断特性。首批人体研究的结果也存在争议。我们使用基于全国计算机的中央登记系统来研究β-肾上腺素能受体拮抗剂和抗抑郁药物使用的累积发生率，以及在3年随访期结束时因重度情感障碍（296，DSM-III-R；F30-F34，ICD-10）导致的残疾抚恤金的时点患病率。我们从一个非常大的数据库（总N = 30485）得出的结果表明，与使用其他β-肾上腺素能受体拮抗剂相比，使用吲哚洛尔与因重度情感障碍导致的残疾抚恤金患病率显著降低（从29%降至52%）相关。与其他β-肾上腺素能受体拮抗剂相比，尤其是与普萘洛尔相比，使用吲哚洛尔时抗抑郁药物的使用率略低。结果表明，在重度情感障碍患者中，吲哚洛尔长期治疗可增强抗抑郁药物（尤其是SSRI）的药理作用。接受吲哚洛尔治疗的患者因重度情感障碍导致的残疾抚恤金患病率较低这一发现表明，对于那些经历过至少一次抑郁发作且正在接受抗抑郁治疗的患者，在治疗心血管疾病时，尽可能将吲哚洛尔作为首选β-肾上腺素能受体拮抗剂使用，可显著降低重度难治性重度情感障碍的患病率。
