Commentary

‘Miracle cures’ in psychiatry?

Current Psychiatry. 2019 September;18(9):13-16

References

1. Freud S. Cocaine papers. In: Freud S, Byck R. Sigmund Freud collection (Library of Congress). New York, NY: Stonehill; 1975;7.
2. Rush AJ. STAR*D: what have we learned? Am J Psychiatry. 2007;164(2):201-204.
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4. Carey B. Fast-acting depression drug, newly approved, could help millions. The New York Times. https://www.nytimes.com/2019/03/05/health/depression-treatment-ketamine-fda.html. Published March 5, 2019. Accessed July 26, 2019.
5. Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. 2016;30(12):1181-1197.
6. Johnson MW, Garcia-Romeu A, Griffiths RR. Long-term follow-up of psilocybin-facilitated smoking cessation. Am J Drug Alcohol Abuse. 2017;43:55-60.
7. Garcia-Romeu A, Griffiths RR, Johnson MW. Psilocybin-occasioned mystical experiences in the treatment of tobacco addiction. Curr Drug Abuse Rev 2014;7(3):157-164.
8. Simon RI. Clinical psychiatry and the law. 2nd ed. Washington, DC: American Psychiatric Press; 1992.
9. Lahti AC, Weiler MA, Tamara Michaelidis BA, et al. Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology. 2001;25(4):455-467.
10. Perrine SA, Sheikh IS, Nwaneshiudu CA, et al. Withdrawal from chronic administration of cocaine decreases delta opioid receptor signaling and increases anxiety- and depression-like behaviors in the rat. Neuropharmacology. 2008;54(2):355-364.
11. Doroshow DB. Performing a cure for schizophrenia: insulin coma therapy on the wards. J Hist Med Allied Sci. 2007;62(2):213-243.
12. Khan A, Kolts RL, Rapaport MH, et al. Magnitude of placebo response and drug-placebo differences across psychiatric disorders. Psychol Med. 2005;35(5):743-749.
13. Singh JB, Fedgchin M, Daly EJ, et al. A double-blind, randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression. Am J Psychiatry. 2016;173(8):816-826.
14. Williams NR, Heifets BD, Blasey C, et al. Attenuation of antidepressant effects of ketamine by opioid receptor antagonism. Am J Psychiatry. 2018;175(12):1205-1215.
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18. Thielking M. Ketamine gives hope to patients with severe depression. But some clinics stray from the science and hype its benefits. STAT. https://www.statnews.com/2018/09/24/ketamine-clinics-severe-depression-treatment/. Published September 24, 2018. Accessed July 26, 2019.
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The compound Freud was describing is cocaine, which we now know is an addictive and dangerous drug that can in fact worsen depression.¹⁰ Another treatment regarded as a miracle cure in its time involved placing patients with schizophrenia into an insulin-induced coma to treat their symptoms; this therapy was used from 1933 to 1960.¹¹ We now recognize that this practice is unacceptably dangerous.

The past is filled with cautionary tales of the enthusiastic adoption of treatments for mental illness that later turned out to be ineffective, counterproductive, dangerous, or inhumane. Yet, the long, arduous journeys our patients go through continue to weigh heavily on us. We would love to offer our patients newer, more efficacious, and longer-lasting treatments with fewer adverse effects.

Discussion: How to best evaluate miracle cures

To help quickly assess a new treatment, the following 5 categories can help guide and organize our thought process.

1. Evidence

What type of evidence do we have that a new treatment is safe and effective? Psychiatric research may be even more susceptible to a placebo effect than other medical research, particularly for illnesses with subjective symptoms, such as depression.¹² Double-blinded, placebo-controlled studies, such as the IV ketamine trial conducted by Singh et al,¹³ are the gold standard for separating a substance’s actual biologic effect from a placebo effect. Studies that do not include a control group should not be regarded as providing scientific evidence of efficacy.

2. Mechanism

If a new compound appears to have a beneficial effect on mental health, it is important to consider the potential mechanism underlying this effect to determine if it is biologically plausible. A compound that is claimed to be a panacea for every symptom of every mental illness should be heavily scrutinized. For example, based on available research, ketamine’s long-lasting effects seem to come from 2 mechanisms^14,15:

Activation of endogenous opioid receptors, which is also responsible for the euphoria induced by heroin and oxycodone.
Blockade of N-methyl-D-aspartate receptors. N-methyl-D-aspartate receptor activation is a key mechanism by which learning and memory function in the brain, and blocking these receptors may increase brain plasticity.

Continue to: Therefore, it seems plausible...

‘Miracle cures’ in psychiatry?

References

Discussion: How to best evaluate miracle cures

1. Evidence

2. Mechanism

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