NSAIDs May be Effective for Depression
Inflammation is hot, both literally and figuratively. The medical literature is replete with studies implicating inflammation as a possible root cause of diseases as varied as heart disease, cancer, Alzheimer’s disease, depression and, of course, arthritis. A recent meta-analysis of all randomized controlled studies for depression yielded some intriguing results.
Researchers scoured the literature and located 14 randomized, placebo-controlled trials assessing the efficacy of anti-inflammatory treatment for depressive symptoms or depression, involving 6,262 participants. Ten trials evaluated the use of non-steroidal anti-inflammatories (NSAIDs) in almost 4,300 patients and four investigated cytokine inhibitors (in just over 2,000 patients). The NSAIDs included celecoxib (Celebrex), ibuprofen, and naproxen, and the cytokine inhibitors included etanercept (Enbrel), adali- mumab (Humira), ustekinumab (Stelara), and infliximab (Remicade). These tonguetwisting cytokine inhibitors are expensive biological agents approved to treat various inflammatory illnesses.
While some studies tested the effects of NSAIDs when added to antidepressants, most were studies primarily of patients with arthritis with depressive symptoms who were treated exclusively with anti-inflammatories. Not all patients met criteria for major depression.
Results. In general, patients assigned to anti-inflammatories improved significantly more than those assigned to placebo. The overall effect size for all treatments was -0.34, which is considered a small to moderate effect. In a subanalysis, the authors found that the single most effective medication was celecoxib when used as an add-on to antidepressants— though this covered only four trials with a total of 132 patients, much fewer than the over 6,000 patients in all studies. The four studies on cytokine inhibitors showed a trend toward an antidepressant effect, but it was not significant. In terms of adverse events, neither the NSAIDs nor the cytokine inhibitors produced more side effects than placebo. However, the studies were relatively short (six to 12 weeks) and some gastrointestinal and cardiovascular side effects sometimes take longer than that to appear (Kohler O et al, JAMA Psychiatry 2014;epub ahead of print).
TCPR’s Take: NSAIDs might be effective in treating depressive symptoms, with effect sizes similar to standard medications, and with no more side effects than placebo. Celecoxib may be particularly promising. If you decide to give these meds a try, here are the doses typically used in the studies reviewed: celecoxib 200 mg to 400 mg a day, ibuprofen 800 mg three times a day, and naproxen 500 mg twice a day. Be careful though: using any of these for depression is off- label, and side effects may emerge over the many months or years of treatment typical in major depression.
Study Shows Relationship between ‘Mini-Strokes’ and PTSD
Transient ischemic attacks (TIAs)— commonly referred to as “mini-strokes”— don’t leave people with any permanent neurological symptoms, but in some individuals they may lead to post-traumatic stress disorder (PTSD) for the event, according to a new study.
The study followed 108 patients who were treated at a German hospital for TIA. Three months after the diagnosis, they were asked to answer a series of questionnaires to self-assess for PTSD, anxiety, depression, quality of life, coping strategies, and medical knowledge. According to the Posttraumatic Stress Diagnostic Scale, 32 patients (29.6%) were classified as having PTSD—a rate 10 times higher than the general German population (prevalence of 2.9%). They also had more depression and anxiety, as well as reduced mental and physical quality of life.
As to why some TIA patients develop PTSD and others do not, researchers said they could not rule out metabolic changes that can occur up to three days after TIA, or the sudden experience of neurological symptoms, which itself may be a major trigger. Other contributors may be the experience of acute pain during the TIA, or the fear that the TIA may be a precursor of stroke.
To prevent the development of PTSD after TIA, researchers recommended prevention efforts, including training patients to develop adaptive coping strategies and briefing them about the realistic stroke risk following a TIA (Kiphuth I et al, Stroke 20l4;45(11):3360-3366).
TCPR’s Take: It’s well known that even a mild stroke can cause psychological consequences such as depression and anxiety. This study shows that TIAs—which are even more “mild,” at least neurologically speaking—can also be sufficiently traumatic to produce PTSD in some patients. While the diagnosis of PTSD in this study was made by a single written questionnaire, the results support the idea that a subset of TIA patients experience significant psychological distress and might benefit from screening and preventive measures.
Personality May Influence the Risk for Alzheimer’s
It’s commonly known that the risk of developing dementia is related to education level, history of head trauma, family history, and genetics. But could personality also play a role? It just might: a group of Swedish and American researchers has found that women who test high on a “neuroticism” scale in middle age may have a higher risk of developing Alzheimer’s disease (AD) later in life.
The research was based on an unusually long-term prospective study (38 years) in which 800 women, ages 38 to 54, were selected at random from the population of a Swedish city in 1968. They were given a full psychological examination at baseline, with subsequent evaluations every six to eight years until 2005.
At baseline, the women were assessed for both neuroticism and extroversion using the Eysenck Personality Inventory. While neuroticism is not a term in common use clinically, in personality research it lives on, and describes people who are anxious, tend to be somaticisers, are emotionally reactive, and are prone to feeling excessively guilty. The extroversion scale measures sociability and positive affect. In addition to these baseline tests, all subjects were evaluated every six to eight years on their level of distress, defined as any stress lasting one month or longer in situations relating to work, health, or family. “Stress” was defined as feelings of irritability, tension, nervousness, fear, anxiety, or sleep disturbances.
During the 38 years of follow-up, dementia was diagnosed in 153 women, 104 of whom had AD. The authors focused on AD because the numbers for other dementias were too small to find any associations.
The upshot of the study is that the most risky combination of personality traits is having high neuroticism and low extroversion. Women with this combination had double the chance of developing AD (16/63, 25%) than those with low neuroticism and high extroversion (8/63, 12.5%). The association between neuroticism and Alzheimer’s was partly mediated by the fact that neuroticism led to a greater degree of subjective distress (Johansson L et al, Neurology 2014;83(17):1538- 1544).
TCPR’s Take: This research shows that “unopposed” neuroticism (that is, neuroticism that isn’t modified by a healthy dose of extroversion) is statistically associated with developing AD. It doesn’t prove that being neurotic causes AD but, rather, that the trait of neuroticism may be simply a precursor of a purely biological disease called Alzheimer’s. So when a middle- aged woman in your practice worries that she will develop dementia, you can reassure her that a positive and extroverted personality reduces her risk. But if she exhibits anxiety, guilt, somatic complaints, and negative affect, this study may give you—and her—more of a reason to work on these symptoms.