KPBS Radio highlighted a new study today by UCSD School of Pharmacy
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In a new analysis published Wednesday in the journal Scientific Reports, UC San Diego researchers said millions of FDA side effect records reveal that people who took ketamine for pain relief reported lower rates of depression.
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“The occurrence of complaints about depression dropped in half after ketamine administration,” said UC San Diego Skaggs School of Pharmacy professor Ruben Abagyan, who led the study.
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The researchers focussed on the FDA’s Adverse Effect Reporting System, a database that tracks negative side effects among people who take various drugs. But the researchers were not primarily interested in bad outcomes.
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Instead, they looked for a positive outcome: declining rates of depression among people taking drugs not typically thought of as antidepressants.
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They found signs that other common drugs — including Botox, a pain reliever called diclofenac and the antibiotic minocycline — also reduced depression among patients in the FDA database.
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[minocycline is a glial modulator and it can prevent CRPS from spreading.]
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University of Miami psychiatry professor Charles Nemeroff wrote that the study was, “very interesting.”
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“The findings are of considerable interest. However the interpretation of the findings are key,” he wrote, saying it will be important to understand whether ketamine is directly treating depression or simply relieving pain, which can indirectly help people experience less depression.
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The UC San Diego researchers said they controlled for this variable by comparing people who took ketamine with those who took other pain medications. They said they still found a larger drop in depression among those who took ketamine.
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This is the open source (free) article in Nature with brief excerpts below:
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.Isaac V. Cohen, Tigran Makints, Rabia Atayee, Ruben Abagyan
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We found that patients listed in the FAERS database who received ketamine in addition to other therapeutics had significantly lower frequency of reports of depression than patients who took any other combination of drugs for pain (LogOR −0.67 ± 0.034) (Fig. 1c). This reduction in depression is specific to ketamine and is known to be much more rapid than current antidepressants, making this observed effect very promising for treatment of patients with acute depressive or suicidal episodes. These patients cannot afford to wait up to six weeks for reductions in their depressive symptoms. Pain reports were also significantly lower for ketamine patients (LogOR −0.41 ± 0.019) (Fig. 1c).
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The analysis of the whole FAERS database revealed several other unintentional depression reducing drugs among antibiotics, cosmeceuticals and NSAIDS (Fig. 2). Our data supported previous studies that observed the psychiatric polypharmacology of minocycline [my emphasis], a tetracycline antibiotic14 (Fig. 2). The NSAID, diclofenac [that has highest incidence of heart attack and cardiac arrhythmia of any NSAID], was also observed to have some antidepressant properties (Fig. 2). It is theorized that both of these drugs may accomplish antidepressant effects through an anti-inflammatory mechanism. Because of the antidepressant activity of several NSAIDs, we further separated the non-ketamine pain cohort. Ketamine patients were then compared to patients who received any other combination of drugs for pain excluding NSAIDs. It was observed that depression event rates remained low (LogOR −0.56 ± 0.035) (Fig. 2)..The reduction of depression rates in ketamine patient records makes a case for study of ketamine as a psychiatric drug. These results imply that ketamine may be further explored as a monotherapy or adjunct therapy for depression. It should also be noted that FAERS data revealed that ketamine use [may] lead to renal side effects and awareness and caution in patients with renal or hepatic impairment may be warranted (Fig. 1a and b). [my emphasis].
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As an important side note, we also evaluated efficacy and side effects with the use of ketamine for pain management. We found that patients who were on ketamine had reduced opioid induced side effects including constipation (LogOR −0.17 ± 0.023), vomiting (LogOR −0.16 ± 0.025), and nausea (LogOR −0.45 ± 0.034) than patients who received any other combination of drugs for pain indications (Fig. 1d). Our data supports ketamine’s opioid-sparing properties and alludes to the fact that patients may receive benefits of improved pain, reduced requirement of opioids, and ultimately less opioid reduced side effects.
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The results of this study support previous small scale studies’ conclusions that ketamine is a good monotherapy or adjunct therapy for depression. In clinical practice ketamine would be especially useful for depression because of the quick onset of its action compared to existing first line therapies. Regardless of the causative mechanism ketamine appears to have therapeutic potential for TRD. Further, the potential to reduce many of the most complained side effects of opioid treatment makes ketamine adjunct therapy for pain seem desirable.
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Overall, this study demonstrates that the therapeutic potential of ketamine can be derived from appropriate statistical analysis of existing population scale data. This study also outlines a methodology for discovering off label pharmacology of existing approved drugs. This method can be applied to other indications and may reveal new important uses of already approved drugs, providing reliable justification for new indications without large investments in additional clinical trials.
