Quetiapine Monotherapy Benefits Range of Depressed Elderly

Jill Stein

September 07, 2011

September 7, 2011 (Paris, France) — Once-daily extended-release quetiapine fumarate monotherapy is significantly more effective than placebo in treating depressive symptoms in elderly patients with major depressive disorder (MDD), regardless of baseline symptoms of anxiety, sleep disturbance, or pain, researchers reported here at the 24th Congress of the European College of Neuropsychopharmacology.

These findings come from a post hoc analysis of an 11-week study showing that flexible-dose extended-release quetiapine monotherapy (50 to 300 mg daily) was effective for the acute treatment of depressive symptoms in adult outpatients 66 years of age and older with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of single-episode or recurrent MDD. Patients also had a Hamilton Depression Rating Scale (HAM-D) total score above 22 and a HAM-D depressed mood score of 2 or higher at enrolment.

Dr. Stuart Montgomery

"There are enormous complaints of depression in the elderly, in the range of 17% to 30%. Of these, it is estimated that a rather small percentage — only 5% — have MDD. The low percentage relates to the difficulty in defining MDD in the elderly. The definition requires that depression interfere with work or social life, but because the elderly don't work, the definition cannot capture the true incidence of MDD in this population," Stuart Montgomery, MD, PhD, emeritus professor of psychiatry at Imperial College in London, United Kingdom, told Medscape Medical News. "We believe that the true incidence is probably higher in older patients, even though the figures commonly cited suggest otherwise."

Elderly patients with MDD frequently experience somatic symptoms, such as sleep disturbances and pain and anxiety symptoms. "Disrupted sleep is probably the most common complaint in depressed elderly, and is often the feature the [general practitioner] should use to ask about other depression symptoms to determine if the patient has depressive illness or not," he said.

Importantly, residual symptoms of both anxiety and sleep disturbance predict early recurrence in elderly patients with MDD, Dr. Montgomery noted.

For these reasons, the researchers decided to study the use of extended-release quetiapine in subgroups of elderly patients with MDD according to baseline anxiety symptoms and baseline levels of sleep disturbance and pain.

Extended-release quetiapine is approved in Europe and the United States as adjunctive treatment for adult patients with MDD who have a suboptimal response to antidepressant monotherapy. In addition, extended-release quetiapine is licensed as a monotherapy for the treatment of MDD in some countries, such as Australia and Canada. The drug is not licensed for generalized anxiety disorder.

Efficacy results reported earlier in 338 patients showed that at week 9, quetiapine (least squares mean [LSM] change, –16.3; P ˂ .001) significantly reduced the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from randomization, compared with placebo (–8.8).

Quetiapine significantly improved all secondary efficacy variables, including the MADRS response rate, HAM-D score, Hamilton Anxiety Rating Scale (HAM-A) score, and Clinical Global Impression–Severity of Illness score change from randomization, compared with placebo, at week 9. The study comprised a 9-week treatment period and a 2-week follow-up period.

Post hoc analyses in a modified intent-to-treat population of 335 patients were conducted in anxiety, sleep disturbance, and pain subgroups.

In patients with anxious depression (baseline HAM-A total score ≥20), a significantly greater improvement in MADRS total score was seen at week 9 with quetiapine than with placebo (LSM change, –17.8 vs –8.5; P ˂ .001). Response rates at week 9 were 65.4% (P ˂ .001) for quetiapine and 27.3% for placebo.

In patients with lower baseline anxiety levels (baseline HAM-A total score ˂20), significant improvements in MADRS total score were seen for quetiapine, compared with placebo (LSM change, –14.8 vs –8.8; P ˂ .001). Response rates at week 9 were 62.8% (P ˂.001) for quetiapine and 33.7% for placebo.

In patients with high levels of baseline sleep disturbance (HAM-D sleep disturbance factor score ≥5), quetiapine significantly improved MADRS total score at week 9, compared with placebo ((LSM change, –17.6 vs –8.7; P ˂ .001). Significantly greater response rates at week 9 were seen with quetiapine than with placebo (66.0% vs 27.5%; P  ˂.001).

In patients with low levels of baseline sleep disturbance (HAM-D sleep disturbance factor score ˂5), quetiapine also significantly improved MADRS total score, compared with placebo (LSM change, –14.4 vs –9.2; P ˂ .001). Significantly greater response rates at week 9 were observed with quetiapine than with placebo (60.9% vs 35.5%; P ˂ .001).

In the subgroup that rated pain 40 mm or higher on a visual analogue scale (VAS), there were significantly greater improvements in MADRS total score at week 9 with quetiapine than with placebo (LSM change, –16.6 vs –8.9; P ˂ .001). Week 9 response rates for quetiapine were significantly greater than those for placebo (65.6% vs 29.0%; P ˂ .001).

In the subgroup that rated pain below 40 mm on a VAS, significantly greater improvements in MADRS total score at week 9 were seen with quetiapine than with placebo (LSM change, –15.7 vs –8.7; P ˂ .001). Response rates at week 9 for quetiapine were 62.0% and for placebo were 32.1% (P ˂ .001).

"The big surprise of our study was to find that quetiapine has such clear-cut efficacy in the elderly, as we have by and large not been able to demonstrate efficacy in the elderly with the conventional SSRIs [selective serotonin reuptake inhibitors], which dominate the antidepressant market," Dr. Montgomery said.

"Fluoxetine, for example, has shown only a 1-point difference on the Hamilton scale between drug and placebo, and was only shown to be effective in a secondary analysis. Sertraline has also shown only a 1-point difference, while we showed a roughly 7-point improvement on the pivotal MADRS scale with quetiapine. While the Hamilton scale is less sensitive, a 1-point change is still only a small effect."

He added: "Our observation that quetiapine has a very strong effect on depression in the elderly and that improvements are maintained when patients are grouped by anxiety, sleep disturbance, and pain demonstrates that the drug should be considered in the elderly with high priority, even if it has to be used in combination with other drugs that don't work."

Dr. David Nutt

"Seventy to 90% of depressed elderly patients report sleep disturbance, about 70% complain of anxiety, and 50% describe pain," said David Nutt, DM, who is Edmund J. Safra professor of neuropsychopharmacology at University College in London, United Kingdom, in an interview with Medscape Medical News.

"SSRI agents are not good for sleep," Dr. Nutt cautioned. "Although they are used to treat anxiety disorders,...for reasons no one understands...some people don't do well on them for anxiety, and they often make anxiety worse to start with."

"They do have an impact on pain, but they're not as good on pain as the noradrenaline reuptake inhibitors," he said. In sum, the adverse effects of SSRIs aggravate sleep [disorders] and anxiety, and this drug [quetiapine] will block those adverse effects."

The study was funded by AstraZeneca. Dr. Montgomery reports receiving honoraria and serving on advisory boards for AstraZeneca, Bionevia, Bristol-Myers Squibb, GlaxoSmithKline, Grunenthal, Johnson & Johnson, Lilly, Lundbeck, Merck, Merz, M's Science Corporation, Neurim, Otsuka, Pierre Fabre, Pfizer, Pharmaneuroboost, Richter, Roche, Sanofi, Sepracor, Servier, Shire, Synonis, Takeda, Theracos, Targacept, Transcept, UBC, Xytis, and Wyeth. Dr. Nutt has disclosed no relevant financial relationships.

24th Congress of the European College of Neuropsychopharmacology (ECNP). Abstract P.2.a.016. Presented September 5, September 2011.

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