NEW YORK (FRONTLINE MEDICAL NEWS)Patients taking daily opioid medication for pain had double the risk of depression over time at dosages of 50 mg or more per day, a new study has shown.

“We already know that depressed patients, over time, take more opioids. But we’ve been questioning whether this high-dose opioid use is really one of the reasons pain patients have higher rates of depression,” Jeffrey Scherrer, Ph.D., said at the annual meeting of the North American Primary Care Research Group.

A previous analysis of Veterans Affairs data conducted by Dr. Scherrer and colleagues demonstrated a risk of new-onset depression over time as opioid exposure increased. However, the retrospective study did not include repeated measures of individual pain severity ( J. Gen. Intern. Med. 2014;29:491-9 ).

So Dr. Scherrer of the department of family and community medicine at Saint Louis University, and his colleagues prospectively studied 355 primary care patients – primarily white, middle-aged women – being treated for chronic low back pain at nine clinics across Texas. Patient levels of depression, pain, anxiety, health-related quality of life, and levels of stress and social support were self-reported at baseline, and at 1 year and 2 years of follow-up.

Information on opioid type and dose, and on comorbid conditions, was collected from patient records and used to assess any association between changes in opioid dosage (0, 1-50 mg, and greater than 50 mg daily) and probability of depression over time, as well as the change in depression levels and the odds of increased opioid dosage.

The adjusted odds ratio of depression over time was 2.65 (1.17-5.98) when opioid dosages increased from 0 to less than 50 mg per day. Although the risk of increased depression with an increase from 1 mg up to 50 mg of opioid per day was marginal (odds ratio, 1.08), the unadjusted odds of developing depression more than doubled (OR, 2.13) when opioid dosage surpassed 50 mg daily. The final adjusted analysis placed the odds ratio of developing depression at 1.65.

But what if patients are depressed because they are in pain or are more susceptible to pain because they are depressed?

“The depression being caused by the pain may be the baseline situation, but the worsening of depression is not due to the pain, it is due to the opioid.” Dr. Scherrer said. “We know that because we have repeated measures of pain, and while the pain remains about the same, the depression keeps going up at each time point. We have an epidemic of new-onset depression being driven by the opioid use, not by the pain.”

Why would a person’s level of pain remain flat despite escalated opioid dosing? Dr. Scherrer said that a previous but unreported history of depression may be making the person more sensitive to pain, and therefore less sensitive to the analgesic effects of the opioids – thus creating a cycle in which they use higher doses of pain medications for longer periods of time.

“If you have a history of depression, you ought to keep your opioids below 50 mg a day,” Dr. Scherrer counseled. “Otherwise, you’re going to jack up your risk of depression.”

The study was supported by the Residency Research Network of Texas Investigators.

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