Phenelzine discontinuation: A bitter pill to swallow

To the Editor

The antidepressant phenelzine (Nardil) joins trifluoperazine (Stelazine) and fluphenazine (Modecate) as the third psychotropic medication to become unavailable in Australia and New Zealand since 2017.

Switching to other psychotropics is complicated, putting the patient at risk of relapse and hospitalisation (Zanker and Ferraro, 2017).

Phenelzine is an irreversible and non-selective monoamine oxidase inhibitor (MAOI) highly effective for treatment of refractory depression (Shulman et al., 2013). Its use is limited by tolerability and dietary restrictions to minimise the risk of hypertensive crisis. Patients who achieve therapeutic response may remain on phenelzine long term (Shulman et al., 2013).

Phenelzine dispensing (60 tablets of 15 mg) has remained stable over the past 16 years, with 6929 prescriptions filled in 2004 and 6419 in 2019 (Figure 1). Tranylcypromine (Parnate), the only remaining MAOI indicated for depression, had 15,214 prescriptions of 20 mg bottles of 50 tablets dispensed in 2019. Although Therapeutic Goods Association approval for importation of phenelzine is possible, it requires a sponsor to complete an extensive application process, there are substantially increased costs for the patient, and ongoing supply isn’t guaranteed.

Figure 1.

MAOI dispensing per calendar year in Australia.

Switching from phenelzine is challenging. Tapering the dose over 4 weeks is recommended to prevent withdrawal reactions. A minimum 2-week ‘wash-out’ period (where dietary restrictions must be maintained) is necessary before starting any new antidepressant to reduce the risk of serotonin syndrome. Rapid switching is potentially risky. If there is an urgent clinical need, it should only be undertaken with stringent clinical monitoring and the availability of medical support. Switching to tranylcypromine may be an option; however, tranylcypromine is associated with more restrictive dietary requirements, increased risk of hypertensive crisis and increased potential for insomnia due to its additional amphetamine-like effects. Some case reports comment on faster switching between tranylcypromine and phenelzine, with reduced wash-out periods (Szuba et al., 1997); however, the evidence for safety with rapid switching from phenelzine to tranylcypromine is less clear.

The discontinuation of trifluoperazine and fluphenazine demonstrated that patients may have relapses leading to hospitalisation while switching to alternative antipsychotics. The risk of relapse when switching from phenelzine is even greater due to the protracted transition process. We call upon the Australian and New Zealand regulatory bodies to take a more considered and proactive approach to ensure continuity of supply of psychotropic medications. Psychotropic prescribers, both specialists and in primary care, as well as patients and carers need timely and comprehensive guidance to manage these risky discontinuation-triggered treatment changes.