Authors' reply.

Sir,

Srivastava et al.[1] describe a 65-year-old woman with recurrent major depressive disorder whose 3-year course of illness showed increasing refractoriness to antidepressant treatment, and whose index (fourth) episode was refractory to two antidepressants despite antipsychotic augmentation. She was subsequently treated with 4 twice-weekly intravenous infusions of ketamine (0.5 mg/kg) administered across 40 min under anesthesiological supervision. Treatment was associated with excellent response; the patient remitted, and remission was maintained with antidepressant monotherapy for at least the following year.

We have two observations related to the management of the case. The baseline Hamilton Rating Scale for Depression score was 17, indicating that depression was mild. Therefore, it could have been appropriate to consider more conventional and approved approaches before resorting to the experimental treatment ketamine. As an example, the patient could have been advised a trial with an antidepressant such as venlafaxine, mirtazapine, or dothiepin; and augmentation, if necessary, could have been accomplished with an atypical antipsychotic drug such as aripiprazole or olanzapine. Next, had ketamine eventually been considered necessary, it could have been more simply dosed by the intranasal route,[2] obviating the inconvenience and discomfort associated with venipuncture.

How is intranasal ketamine administered? Ketamine solution (50 mg/ml) is loaded into an aerosol canister that ejects 0.1 ml/spray. Therefore, each 0.1 ml dose from the aerosol will contain 5 mg of ketamine. In a hypothetical woman who weights 60 kg, a 0.5 mg/kg dose translates to a total requirement of 30 mg of ketamine, or 6 sprays. Administering these 6 sprays at approximately 7 min intervals will result in the total dose being dispensed across approximately 35–40 min.

At the time of administration of the spray, the patient will need to lie down; else, the dose sprayed into the nostril may run downward and out of the nose. The patient should also be instructed not to “sniff” and “pull” the contents of the spray deeper into the nose; else, it may be pulled into the throat and be swallowed (with subsequent poor absorption). Allowing the dose to remain in the nasal mucosa results in absorption into the rich nasal vascular bed and possible direct transmission to the brain along the olfactory pathways through the cribriform plate of the ethmoid bone.[2]

The patient can sit up and even move around once the sprayed dose has been absorbed, before the next spray in that session is due. General precautions that need to be observed, such as cardiovascular monitoring and posttreatment monitoring for 2–4 h, are as with intravenous ketamine protocols.

Intranasal ketamine has been studied in a randomized, placebo-controlled crossover trial,[3] and has been administered in adolescent and adults as maintenance therapy for years.[24] Like intravenous ketamine infusion, intranasal ketamine is emphatically an experimental procedure that should not be lightly undertaken. However, it could prove to be a useful resource as an emergency procedure for patients who are suicidal. It may even be preferable over intravenous ketamine in patients with refractory depression. It is acknowledged, however, that intranasal ketamine has not been as well studied as intravenous ketamine infusion.

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