Institute of Psychiatry, University of Bologna, Italy.
J Clin Psychopharmacol. 2013 Aug;33(4):565-9. doi: 10.1097/JCP.0b013e3182905967.
Late-life depression, often in association with anxiety, affects approximately 15% of individuals older than 65 years. Selective serotonin reuptake inhibitors are the first-line treatment but could be responsible of an early exacerbation of anxiety, possibly reduced by a very gradual titration of drugs. The main aim of this study is to compare gradual and rapid (standard) titration of paroxetine in an elderly population.
In a naturalistic setting, 50 elderly (≥60 years old) outpatients with unipolar mood disorder or anxiety disorder were naturalistically assigned to abrupt initiation of 10 mg of paroxetine or to a gradual increase with 2.5 mg on alternate days up to 10 mg in 7 days. Then dosage could be maintained at 10 mg or increased according to clinical response. Primary outcome was efficacy as assessed by the Hamilton Depression Rating Scale (HAM-D) 21, HAM-D symptom subscales (core, psychic anxiety, somatic anxiety cluster), and Hamilton Anxiety Rating Scale changes. Secondary outcome was evaluation of overall dropouts at eighth week and evaluation of most common adverse effects through the global judgment of the Dosage Record and Treatment Emergent Symptom Scale. All data were recorded weekly for the first 8 weeks of treatment (with 1 more evaluation after 3 days from the baseline).
Samples were comparable at baseline, with patients in gradual titration showing a higher level of psychic anxiety. During the first 3 days of treatment, a significant worsening in psychic anxiety was observed in patients treated abruptly with 10 mg of paroxetine (difference in HAM-D psychic anxiety subscale from baseline: 110.61% vs 89.38% with rapid and slow titration, respectively; t test P = 0.03). Overall, a significantly greater improvement in depressive and anxious symptoms favored gradual titration (HAM-D core cluster and HAM-D psychic anxiety cluster, respectively, P = 0.014 and P < 0.001, also when controlling for confounders). At the eighth week, significant higher dropouts in patients administered with abrupt dosage was observed (12.00% vs 40.91%, P = 0.02, respectively for slow and rapid titration).
Our results suggest that a gradual titration of paroxetine could avoid the initial treatment anxiety worsening and dropout at the beginning of the treatment.
老年期抑郁症，常伴有焦虑，影响约 15%的 65 岁以上人群。选择性 5-羟色胺再摄取抑制剂是一线治疗药物，但可能导致焦虑早期恶化，通过非常缓慢地滴定药物可能会减轻。本研究的主要目的是比较帕罗西汀在老年人群中的逐渐滴定和快速（标准）滴定。
在自然环境中，50 名患有单相心境障碍或焦虑障碍的老年（≥60 岁）门诊患者被自然分配为立即开始服用 10mg 帕罗西汀或每隔一天服用 2.5mg 递增至 7 天内达到 10mg。然后可以维持 10mg 的剂量或根据临床反应增加剂量。主要疗效指标为汉密尔顿抑郁量表（HAM-D）21 评分、HAM-D 症状子量表（核心、精神焦虑、躯体焦虑簇）和汉密尔顿焦虑量表的变化。次要结局是第八周总体脱落率的评估和通过剂量记录和治疗出现症状量表的整体判断评估最常见的不良反应。所有数据在前 8 周每周记录一次（在基线后 3 天再评估 1 次）。
两组在基线时具有可比性，逐渐滴定组患者的精神焦虑程度较高。在治疗的前 3 天，快速滴定组患者的精神焦虑明显加重（HAM-D 精神焦虑子量表从基线的差异：分别为 110.61%和 89.38%；t 检验 P=0.03）。总的来说，逐渐滴定组在抑郁和焦虑症状上有显著的改善（HAM-D 核心簇和 HAM-D 精神焦虑簇，分别为 P=0.014 和 P<0.001，即使在控制混杂因素后也是如此）。在第八周时，快速滴定组患者的脱落率明显更高（分别为 12.00%和 40.91%，P=0.02）。
我们的结果表明，帕罗西汀的逐渐滴定可以避免治疗开始时的初始治疗焦虑恶化和脱落。
