An 8-week, Open-label Study to Evaluate the Effect of Sertraline on Polysomnogram in Depressive Patients With Insomnia

Official Title: “An 8-week, Open-label Study to Evaluate the Effect of Sertraline on Polysomnogram in Depressive Patients With Insomnia”

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 macroarchitecture. Many all-night PSG studies have shown atricyclic 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.

Intervention(s) in this Clinical Trial

• Drug: sertraline
  • sertraline: 10-80mg/day

Primary Measures

• the effect of sertraline on suppressing the percentage of REM sleep in depressive patients with insomnia as mono-therapy
  • Time Frame: 56 days
    Safety Issue?: Yes

Secondary Measures

• the effect of sertraline on sleep continuity and SWS as mono-therapy
  • Time Frame: 56 days
    Safety Issue?: Yes
• the correlation between the degree of REM suppression with the degree of clinical improvement in the treatment of sertraline as mono-therapy.
  • Time Frame: 56 days
    Safety Issue?: Yes

Inclusion Criteria:

For inclusion in the study patients must fulfil all of the following criteria:

• 1. Provision of written informed consent by patient or his/her legal guardian
• 2. Hospitalised for a diagnosis of major depressive disorder by DSM-IV (296.2X, 296.3X)
• 3. HRSD score>18
• 4. Total score of sleep disturbance factor in HRSD (items 4, 5, and 6; score range, 0-6)>3
• 5. Females or males, and aged 18 to 65 years
• 6. Able to understand and comply with the requirements of the study

Exclusion Criteria:

Any of the following is regarded as a criterion for exclusion from the study:

• 1. Pregnancy or lactation
• 2. Any DSM-IV Axis I disorder, except for major depressive disorder
• 3. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
• 4. Known intolerance or lack of response to sertraline, as judged by the investigator
• 5. Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir
• 6. Use of any of the following cytochrome P450 3A4 inducers in the 14 days preceding enrolment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids
• 7. Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation
• 8. Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria
• 9. Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrolment
• 10. Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
• 11. Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension) as judged by the investigator
• 12. Organic change was founded by brain CT
• 13. Involvement in the planning and conduct of the study
• 14. Previous enrolment or randomisation of treatment in the present study
• 15. Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
• 16. An absolute neutrophil count (ANC) of 1.5 x 109/L
• 17. Sleep disorder such as Apnea and Hyponea Syndrome, PLMS and narcolepsy
• 18. The work time is rotate and/or often flies across the time zone
• 19. Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs)
• 20. Concomitant use in patients taking pimozide

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Guang Dong Provincial Mental Health Institute Other

Overall Clinical Trial Officials and Contacts

Bin Zhang, M.D&Ph.D Principal Investigator Guang Dong Provincial Mental Health Institute  

Information obtained from ClinicalTrials.gov on February 02, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01032434

Study ID Number: WS 458774

ClinicalTrials.gov Identifier: NCT01032434

Health Authority: China: Ethics Committee