Major depressive disorder (MDD) is characterized by persistent sadness, hopelessness, and loss of interest in usual activities [1]. Other common symptoms include [2]:
- Fatigue and decreased energy
- Sleep disturbances
- Appetite changes and weight fluctuations
- Difficulty concentrating and making decisions
- Physical symptoms like headaches or digestive issues
- Feelings of worthlessness and guilt
- Recurrent thoughts of death or suicide
These symptoms significantly impair social, occupational, and daily functioning. MDD episodes typically last at least 2 weeks and often persist for years or decades.
Therapeutic ketamine has shown promising effects for rapidly alleviating MDD symptoms as a short-term intervention and combined with other treatments for longer-term remission. Moreover, ketamine usually treats the underlying syndrome (e.g., PTSD/CPTSD), which is rarely improved by conventional antidepressants.
Multiple studies have found significant improvement in depressive symptoms within hours after a single low-dose ketamine infusion, with effects lasting about 7 days on average [3][4]. The rapid antidepressant effects are unlike traditional antidepressants, which take 4-6 weeks to work.
Repeated ketamine infusions extend the antidepressant effects. One study found that 70% of patients with treatment-resistant depression experienced sustained remission for over 3 months following 6 ketamine infusions [5].
For longer-term recovery, ketamine is often provided alongside psychotherapy and traditional antidepressants. This combines the rapid relief of ketamine with techniques to maintain benefits [6].
The ketamine literature, both academic and lay alike, consistently tout this drug for treatment-resistant depression. Giving the impression, if not asserting explicitly, that a diagnosis of TRD is a prerequisite to a trial of ketamine. We hold that this assistance on a TRD diagnosis is nonsense.
If ketamine is proven to be effective for TRD, why should we imagine that it’s any less effective on MDD cases that are treatable with conventional antidepressants? What’s the rationale?
If it were the case – it certainly is not – that conventional antidepressants were more effective than ketamine, then it could make sense to try conventional first, leaving ketamine as a last resort. But the opposite is the case. Ketamine is effective for 60+% of cases, while conventional antidepressants are only 30% effective.
Psychiatrists – according to the standard-of-care – prescribe one conventional antidepressant after another to a treatment-resistant patient, hoping that the next one will turn the trick. This protocol only increases the probability of success marginally. E.g., 30% for the first conventional, 6% for the second, 3% for the third and so forth. (These figures are for illustration only.) It makes no sense to eschew ketamine with a 60+% effective rate as the preferred first trial.
In summary, ketamine can rapidly reverse depressive symptoms and bring relief to patients struggling with MDD. It represents an exciting new approach for managing this debilitating acutely and over the long term.
References:
[1] American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596
[2] CDC. (2018, February 26). Learn About Mental Health – Depression. CDC. https://www.cdc.gov/mentalhealth/learn/index.htm.
[3] Berman RM, Cappiello A, Anand A, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47(4):351-354. doi:10.1016/s0006-3223(99)00230-9
[4] Murrough JW, Iosifescu DV, Chang LC, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013;170(10):1134-1142. doi:10.1176/appi.ajp.2013.13030392
[5] Phillips JL, Norris S, Talbot J, et al. Single, Repeated, and Maintenance Ketamine Infusions for Treatment-Resistant Depression: A Randomized Controlled Trial. Am J Psychiatry. 2019;176(5):401-409. doi:10.1176/appi.ajp.2018.18070834
[6] Abdallah CG, Sanacora G, Duman RS, Krystal JH. Ketamine and rapid-acting antidepressants: a window into a new neurobiology for mood disorder therapeutics. Annu Rev Med. 2015;66:509-523. doi:10.1146/annurev-med-053013-062946