An 8-week, Open-label Study to Evaluate the Effect of Sertraline on Polysomnogram in Depressive Patients With Insomnia
Condition: Depression
MeSH terms: Depression
Study type: Interventional

Summary: 
      Major depressive disorder is associated with several sleep Polysomnograph (PSG) findings: (1)
      impaired sleep continuity; (2) non-REM (NREM) changes; and (3) enhanced rapid eye movement
      (REM) sleep. The first two patterns are common in other psychiatric disorders, while the REM
      pattern is very characteristic in depression, so the phase-advance theory was accepted by
      most of psychiatrists. Many researchers have focused on the biological rhythm to investigate
      the etiological and pathophysiology of depression, and they think depression can be cured if
      its sleep abnormality is ameliorated.

      It is well known that most of antidepressants treat depression through 5-hydroxytryptamine
      (5-HT) neurons. 5-HT also affects the regulation of the sleep-wake cycle and the sleep
      microarchitecture. Many all-night PSG studies have shown tricyclic antidepressants can
      ameliorate the sleep architecture abnormality in depression by producing rapid suppression of
      REM sleep.

      Compared to TCAs, SSRIs are generally less sedating because of its high selectivity for
      serotonin receptors. SSRIs can suppress REM sleep and delay REM latency too, but they
      increase awakenings and reduce SWS at the same time. One PSG study shown sertraline minimally
      increases sleep efficiency and reduces nocturnal wakefulness time, which may benefit
      depressive patients. However, this study compared the sleep architecture before and after 12
      weeks of pharmacotherapy, so the tolerance to the disturbance of sleep architecture in
      antidepressants appears to develop over several weeks of treatment. Sertraline has a greater
      potency against 5-HT reuptake as well as better selectivity for 5-HT reuptake relative to NE
      reuptake than any other SSRIs, and the relative selectivity of sertraline for inhabiting 5-HT
      reuptake relative to DA reuptake is somewhat less than of any other SSRIs. So it has chance
      to exhibit better effect on sleep architecture in depressive patients.

      Finally, it is difficult to be determined that the unique phenomenon of sertraline is its
      genuine characteristics or the tolerance after 12-week treatment, so it is crucial to assess
      the effect of sertraline on sleep architecture in acute treatment. We hypothesized that
      sertraline could suppress the REM sleep, and have little damage to the sleep architecture of
      depressive patient.
    

Detailed description: 
      [Abstract] Purpose of the study: To evaluate the effect of sertraline on polysomnographic
      (PSG) variables and clinical improvement in the treatment of depressive patients with
      insomnia. Methods used: The study design was 8-week and open-label trial. Patients were
      diagnosed as major depressive disorder. Their Hamilton Rating Scale for Depression (HRSD)
      score was more than 18, and HRSD-sleep disturbance score was more than 3. After 7-day
      wash-out period and 2 nights PSG (the first night as adaptive and the second night as
      baseline), 31 depressive patients were administered by sertraline as 50 mg in 8 am in the 1st
      day. The dosage of sertraline would be titrated during the 8-week treatment, and the maximum
      was lower than 200 mg/day. The primary endpoints were the changes of PSG variables from
      baseline to the 56th Day. The secondary endpoints were the changes of subjective sleep
      quality and clinical performance from baseline to the 56th Day. Their sleep quality was
      evaluated with Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI), and
      their clinical performance was evaluated with HRSD and Clinical Globe Impression (CGI).
      Summary of results containing real data and appropriate statistical assessments: The
      Intent-to-Treat analysis included 31 subjects. The final dosage was titrated as 130.6±47.8
      mg/day. The Rapid Eye Movement (REM) sleep latency was prolonged significantly in the 1st day
      and throughout 8-week treatment. The percentage of REM sleep decreased significantly in the
      1st day, but increased gradually along the following treatment. AI reached the highest level
      in the 1st day (13.8±7.2), and decreased along the following treatment. SL decreased
      significantly and reached normal range (<30minutes) after the visit of 14th day. The
      percentage of stage 3 increased gradually, and became higher in the 14th, 28th, 56th days.
      HRSD score was similar between baseline and the 1st day, and became significantly lower in
      the 14th, 28th, and 56th day. Similar pattern was shown in CGI. Scores of HRSD-sleep
      disturbance, PSQI, ESS decreased gradually throughout the treatment. The sleep latency in
      multiple sleep latency test maintained stable throughout treatment. The reducing score rates
      of HRSD and CGI-GI significantly correlated with the reducing score rate of REM latency in
      all visits, and they also significantly correlated with sleep latency, sleep efficiency, and
      stage 3 in some visits. Further, significant correlation was shown between the reducing score
      rate of HRSD in the 56th day and the the reducing score rate of REM latency in the 1st day
      (r=-0.733, P=0.003). Conclusions: Sertraline was an effective antidepressant, and its
      effectiveness had relationship with the reduction of REM latency during the 8-week treatment.
      Further, the final clinical improvement could be predicted by the extent of shorten REM
      latency in the first night. So the suppression of REM sleep might be the key mechanism of
      antidepressive[1]. On the other hand, Sertraline had little alerting property without sleep
      disturbance in the treatment[2]. This property of sertraline must benefit the remission of
      depression, and the remission contributed the sleep improvement in turn. It was virtuous
      cycle in depressive treatment.
    

Intervention name(s): sertraline
Intervention type(s): Drug
Intervention description(s): sertraline: 50-200mg/day
Other intervention name(s): zoloft
Intervention MeSH terms: Sertraline
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: sertraline; Polysomnograph