Antidepressants Work and Don't Boost Suicide Risk: Studies

Contrary to what has been feared, the antidepressants known as serotonin reuptake inhibitors (SSRIs) are initially effective in as many as one-third of depressed patients and don't appear to increase the risk of suicide, two new studies claim.

The reports, both of which were funded by the National Institute of Mental Health, appear in the January issue of the American Journal of Psychiatry.

The suicide findings seem to challenge a 2004 advisory by the U.S. Food and Drug Administration that warned that suicidal behavior may increase after treatment with SSRIs. However, the study did find that suicide attempts were higher among teens than adults, a finding borne out by other research.

The first report is based on early data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, the largest study of its kind. This research looked at the benefits of antidepressants in "real world" settings.

"About a third of the patients achieved remission," said lead researcher Dr. Madhukar Trivedi, director of the Mood Disorders Research Program and Clinic at the University of Texas Southwestern Medical Center, in Dallas. "An additional 10 to 15 percent achieved a response."

The object of the study was to provide physicians with guidelines for treating depression, Trivedi said. "The goal is to have patients provided with an adequate dose of medication for an adequate time," he explained. "Treatment would be tailored for each individual patient to get the most benefit from treatment."

For the study, researchers looked at the results of prescribing the SSRI Celexa to 2,876 patients with major depression. These patients also had other physical and psychological problems. The researchers found that about a third of the patients had their depression cured during the first 12 weeks of treatment.

In addition, another 10 percent to 15 percent of the patients showed a response to the medication, or reduction of at least half their symptoms. For patients who did not improve, later phases of the trial will use other medications or combinations of medications to see what might help those who did not benefit from the drug used in the first phase of the trial.

"These antidepressants in routine clinical care produce outcomes comparable with what is seen in research settings," Trivedi said. "These treatments do work in routine clinical care. There also has to be careful monitoring of side effects. In addition, you have to monitor dose and duration of the treatment, based on the patient's progression."

One expert thinks this study will eventually provide guideposts for treating depression that physicians can follow.

"This study, when it is all finally published, will give us a very good idea of how to treat treatment-resistant depression, and what the next step is after the SSRI fails," said Dr. David L. Dunner, director of the University of Washington's Center for Anxiety and Depression.

In the second study, researchers found the risk of suicide attempts and of successful suicides actually dropped in the weeks following the start of SSRI therapy.

"The risk of a serious suicide attempt in people who start taking antidepressant medication is, fortunately, quite low -- less than one in 1,000," said lead author Dr. Greg Simon, a researcher at the Group Health Cooperative, in Seattle. "The risk actually goes down after people start antidepressant medication."

The study also found no increase in suicide risk with the newer antidepressants, such as SSRIs, Simon added. "If anything, our data suggests that with the newer antidepressants there is less risk than with the older antidepressants," he said.

For the study, Simons's team collected data on 65,103 patients who had prescriptions for antidepressants between 1992 and 2003.

The researchers found the number of suicide attempts dropped by 60 percent in adults in the first month after starting treatment. The suicide rate continued to drop in the succeeding five months.

Among all the patients, there were 31 suicides in the six months after starting antidepressant therapy. That rate did not change from one month after starting treatment or in subsequent months.

However, teens had more suicide attempts than adults. Simon's group found that in the first six months of antidepressant treatment, the suicide rate was 314 attempts per 100,000 in teens, vs. 78 attempts per 100,000 in adults. For teens and adults, the rate was highest in the month before treatment and dropped by about 60 percent after treatment began, the researchers found.

In its 2004 warning, the FDA said people taking antidepressants should be closely monitored because of the risk of suicide.

"People should be closely monitored, but not because these drugs are especially risky," Simon said. "The real problem in the treatment of depression is that people start medicine and the medicine has side effects or the medicine doesn't work right away, and they get discouraged and they drop out."

Dunner agreed that close monitoring is essential when prescribing patients antidepressants. "Monitoring depression is very important," he said. "Often people come in for treatment when they are starting to get worse."

Monitoring is needed more for side effects from the drugs than to watch for suicidal behavior, Dunner said. "Suicide is a pretty rare event," he said. "It is more important to monitor for side effects and adherence to the medication."

More information

The American Academy of Family Physicians can tell you more about antidepressants.

Patients' Requests For Antidepressants Can Influence Physician Evaluation Of Depression

Patients who initiate a general discussion about the need for antidepressant medication with their primary care physician are more likely to be thoroughly evaluated for depression than those who make a brand-specific request or no request, according to a new study in the December issue of Medical Care.

The study also found that general requests for antidepressants increased the likelihood that patients would be screened for the existence of suicidal acts or impulses.

The research was led by an investigator at the University of California, San Francisco (UCSF) in collaboration with researchers from the University of California, Davis and the University of Rochester.

In a previous study, the first controlled investigation of its kind, the research team had examined the clinical behavior of physicians faced with a patient request for antidepressant treatment. From this earlier study and others, the scientists found that patients' requests had a profound effect on physician prescribing habits regarding both major depression and the psychological condition known as adjustment disorder, which involves depression and anxiety in response to pain or a major event, such as illness or divorce, according to lead author Mitchell Feldman, MD, MPhil, professor of medicine at UCSF, and an internist at UCSF Medical Center.

"Our new research extends those findings by examining the impact of patient requests on the level of history-taking carried out by the physician and by exploring the association of history-taking with diagnostic accuracy as well as provision of acceptable initial care for depressed patients," he said.

The study was conducted with 18 "standardized patients" -- actors who are specifically trained to portray patients in medical education settings. Each "patient" portrayed a role involving one of two clinical presentations: major depression accompanied by carpal tunnel syndrome or an adjustment disorder accompanied by low back pain. The standardized patients were also trained to request an anti-depressant medication by brand name, or request a general anti-depressant, or not ask for medication.

A total of 298 visits to 152 internists and family physicians in four health care organizations in California and New York took place during the study. The physicians did not know that their appointments were with standardized patients as opposed to real patients, but they did give their permission to be part of the study and were told that the visits were audio recorded and would be examined for content following each interaction.

The researchers studied physician history-taking patterns, examining whether a diagnosis of depression was placed in the medical record, the length of the visit, and whether minimally acceptable initial depression care had been provided. Minimally acceptable depression care is defined as any combination of the following steps -- prescribing an antidepressant prescription, providing a mental health referral, or giving a follow-up visit within two weeks of the initial visit.

Study findings showed that requests for general antidepressant medication were associated with an increase in depression-specific history-taking by physicians. On average, physicians asked 0.80 more questions than if no request was made, while brand-specific requests were only marginally associated with an increase in questions (0.45 more questions).

"It may be that physicians see a request for a general medication as an invitation for further discussion about the diagnosis and treatment options, whereas brand-specific requests may be heard as a consumer demand for medical services in response to emotional persuasion rather than high-quality information," said Feldman.

A greater amount of time spent by the physician in depression history-taking was also directly associated with both the likelihood of a diagnosis of depression being made in the patient's medical record and the provision of minimally acceptable initial depression care.

Findings also showed that physicians obtained more extensive depression-related history from patients who portrayed major depression with carpal tunnel syndrome compared to those who portrayed an adjustment disorder accompanied by low back pain (6.7 questions compared to 5.2 questions).

Patient requests for medication did not appear to distract physician attention from treating the coexisting musculoskeletal conditions presented by patients in the study, and the researchers found no evidence to support the assertion that requests reflecting direct-to-consumer advertising distract the physician from taking a complete medical history. Instead, the research team concludes that a patient request for medication serves to increase the thoroughness of depression history-taking, including inquiries about suicide.

"Patients should be educated advocates for their own quality health care, but if they become over-focused on wanting a particular treatment rather than the most appropriate treatment in general, the result may be missed opportunities and diminished quality of care," Feldman added.

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The study was supported by a grant from the National Institute of Mental Health.

UCSF is a leading university that advances health worldwide by conducting advanced biomedical research, educating graduate students in the life sciences and health professions, and providing complex patient care.

Contact: Vanessa deGier
University of California - San Francisco