Anti-Inflammatory Treatments Look Promising for Bipolar Depression

July 1, 2016 · Posted in Potential Treatments · Comment 

anti-inflammatories may help bipolar depression

Inflammation has been linked to both unipolar and bipolar depression. New research shows that anti-inflammatory treatments may reduce bipolar depression, for which few treatments exist.

Researchers led by Jonathan Savitz divided people with bipolar depression into four groups. One group received two placebos, another received minocycline (a drug with neuroprotective and immune-modulating properties) plus a placebo, the third received aspirin plus a placebo, and the final group received both minocycline and aspirin. Of the 64 participants, those who took both minocycline and aspirin were most likely to respond to treatment and to enter remission. In people with body mass indexes (BMIs) above the median of 30, a sign of greater inflammation, 100% of those who received both anti-inflammatory drugs responded to treatment, compared to 36% of those who received aspirin alone, 33% of those who received minocycline alone, and 25% of those who received two placebos.

Dosages of the drugs were 100mg twice a day for minocycline and 81mg twice a day for aspirin. Savitz and colleagues believe that aspirin and minocycline must work particularly well together, and are modifying their study to more directly compare use of the two anti-inflammatory drugs together to the absence of anti-inflammatory treatments.

Blood and Now Brain Inflammation Linked to Depression

September 16, 2015 · Posted in Brain Imaging, Risk Factors · Comment 

microgliaThere is growing evidence of a link between inflammation of depression. At the 2015 meeting of the Society of Biological Psychiatry, researcher Jeff Meyer summarized past studies on inflammatory markers. These are measurements, for example of certain proteins in the blood, that indicate the presence of inflammation in the body.

Common inflammatory markers that have been linked to depression include IL-6, TNF-alpha, and c-reactive protein. At the meeting, Meyer reviewed the findings on each of these. Twelve studies showed that IL-6 levels are elevated in the blood of patients with depression. Four studies had non-significant results of link between IL-6 and depression, and Meyer found no studies indicating that IL-6 levels were lower in those with depression. Similarly, for TNF-alpha, Meyer found 11 studies linking elevated TNF-alpha with depression, four with non-significant results, and none showing a negative relationship between TNF-alpha and depression. For c-reactive protein, six studies showed that c-reactive protein was elevated in people with depression, six had non-significant results, and none indicated that c-reactive protein was lower in depressed patients.

Most studies that have linked inflammation to depression have done so by measuring inflammatory markers in the blood. It is more difficult to measure inflammation in the brain of living people, but Meyer has taken advantage of new developments in positron emission tomography (PET) scans to measure translocator protein binding, which illustrates when microglia are activated. Microglial activation is a sign of inflammation. Translocator protein binding was elevated by about 30% in the prefrontal cortex, anterior cingulate cortex, and insula in study participants who showed symptoms of a major depressive episode compared to healthy control participants. The implication is that the depressed people with elevated translocator protein binding have more brain inflammation, probably via microglial activation.

The antibiotic minocycline reduces microglial activation. It would be interesting to see if minocycline might have antidepressant effects in people with depression symptoms and elevated translocator protein binding.

Another promising open study of minocycline in bipolar depression

September 12, 2014 · Posted in Potential Treatments · Comment 

Dreaming Young African Man

Joanna Soczynska in Roger McIntyre’s lab at the University of Toronto presented a poster at the 2014 meeting of the International College of Neuropsychopharmacology (CINP) on the anti-inflammatory and neuroprotective antibiotic minocycline.

Twenty-seven patients with a major depression received minocycline in addition to the medications they were already being prescribed. Dosage was 100mg twice a day. Treatment with adjunctive minocycline was associated with significant improvement on several scales that measure depression severity.

Editor’s Note: What was particularly interesting was that a subset of patients achieved complete remission, raising the question whether these patients might have markers of inflammation that would predict this excellent response. The authors concluded that the “results provide a rationale for testing minocycline’s efficacy in a larger randomized, placebo-controlled trial.” 

Exactly this type of study was proposed a year ago by researcher Andy Nierenberg and given the best marks by a National Institute of Mental Health review committee but was turned down for funding because the National Institute of Mental Health has implemented a new initiative, Research Domain Criteria (RDoC), that lays out new criteria for research, limiting funding to those studies that focus on a molecular target that spans several diagnoses.)

Antibiotic Minocycline Could Improve Bipolar Depression

August 7, 2013 · Posted in Potential Treatments · Comment 

depressed young man

In an abstract presented at the 2013 meeting of the Society of Biological Psychiatry, Iosifescu et al. reported that the antibiotic minocycline, which has showed anti-inflammatory, neuroprotective, and mitochondrial-sparing effects in animal models, brought about improvement in patients with bipolar depression. Doses of 100mg to 300mg per day were successful in this small open study.

There are some positive placebo-controlled data in patients with schizophrenia who were prescribed this antibiotic. However, until now it had not been studied in bipolar disorder. The preliminary data reported here suggest that controlled double-blind studies of this agent are needed in bipolar depression.

The abstract (#497) can be found in the 2013 convention supplement (9S) to the journal Biological Psychiatry.

 

Inflammation and Oxidative Stress in Bipolar Disorder

January 6, 2011 · Posted in Current Treatments, Neurobiology, Potential Treatments · Comment 

A number of studies presented at the 4th Biennial Conference of the International Society for Bipolar Disorders conference in Sao Paulo, Brazil in March reported new data relevant to inflammation and oxidative stress. Both inflammation and oxidative stress increase risk of cardiovascular disorders, and patients with inadequately treated mood disorders lose 10 or more years of life expectancy from cardiovascular disorders compared to the general population. Inflammation and oxidative stress may also contribute to the symptoms, evolution, and progression of the mood disorders themselves.

It is possible that these two processes could become new targets for therapeutic intervention in addition to more traditional psychopharmacological drugs that primarily target the neurotransmitters dopamine, norepinephrine, serotonin, and the neurotrophic factor BDNF. Read more