Reversible cerebral vasoconstriction syndrome and treatment with monoamine oxidase inhibitor

Reversible cerebral vasoconstriction syndrome (RCVS) is an acute neurovascular condition characterized by severe headaches, with or without focal neurological deficits or seizures, and segmental constriction of cerebral arteries that resolves within 3 months (Calabrese et al., 2007; Call et al., 1988; Ducros et al., 2007; Ducros, 2012). The severe pain usually lasts 1–3 hours, but thunderclap headaches usually recur, with an average of four attacks within 1–4 weeks. The major complication of RCVS is stroke that can be either ischaemic or haemorrhagic, and may rarely lead to unfavorable neurological outcome or death (Calabrese et al., 2007; Ducros, 2012).

RCVS is increasingly recognized and seems to be not so rare, as suggested by a French prospective monocentric study in which 67 cases were recruited in 3 years (Ducros et al., 2007). It is tentatively attributed to an acute deregulation of cerebral arterial tone control with sympathetic overactivity (Ducros, 2012). In about 50% of the cases, RCVS is precipitated post partum or by exposure to various vasoactive serotoninergic or adrenergic substances, including cannabis, selective serotonin-reuptake inhibitors, and nasal decongestants (Noskin et al., 2006).

The management of RCVS involves removal of any vasoactive substance, rest, and prescription of nimodipine, a calcium-channel blocker, in order to improve the cerebral vasoconstriction (Lu et al., 2004). Here, we report the case of a young woman suffering from a major depressive disorder treated by monoamine oxidase inhibitor (MAOI), who developed a RCVS. To our knowledge, this is the first reported case of RCVS induced by MAOI.

A 22-year-old woman who suffered from a severe major depressive disorder with a 3-year history of recurrent episodes (including three episodes and four hospitalizations) was presented to our service. Her last episode lasted for approximately 1 year. A range of treatments were prescribed including escitalopram 10–20 mg, mirtazapine 30–60 mg, venlafaxine 75–300 mg, clomipramine 150 mg with mianserin 60 mg, but all proved to be ineffective. The young woman recovered with the MAOI iproniazid 75 mg, which is a recommended treatment for resistant depressive disorder (Adli et al., 2003). She relapsed 1 year later after a switch from iproniazide to venlafaxine 300 mg in combination with quetiapine 200 mg. This switch was prompted by a nationwide withdrawal of iproniazid stocks in France. Her clinical condition worsened with an increase in suicidal thinking, which resulted in further hospitalization. After 2 weeks of wash out, a prescription of phenelzine, another MAOI, was initiated and increased up to 90 mg. Three weeks after phenelzine initiation, she complained of a sudden excruciating headache that peaked within 1 min, like a thunderclap, and lasted 45 min. She was transferred to an emergency department. Clinical and neurological examination was normal, with a supple neck. Plain cerebral CT scan and routine blood tests and lumbar puncture were normal. Brain magnetic resonance imaging (MRI) with angiography showed no abnormalities. A computed tomography cerebral angiography (CTA), 2 days after the MRI, revealed diffuse, multifocal, segmental narrowing involving large and medium-sized arteries in the anterior and posterior circulations, with occasional dilated segments, like “strings and beads” (Figure 1A and B), suggestive of RCVS. Phenelzine was immediately stopped and nimodipine 120 mg daily along with paracetamol was started. During the 8-day hospitalization, the patient had only one headache recurrence without any other neurological manifestations. Following discharge from the neurology department, she was transferred back to our psychiatric department because of severe depression. A follow-up CTA 1 month later revealed a complete disappearance of cerebral vasoconstriction (cf. Figure 1C and D). Subsequent antidepressant strategy was thoroughly discussed. Electroconvulsive therapy was not considered given the risk of intracranial hypertension. Given the severity of the current episode of depression, it was decided to begin a course of i.v. clomipramine, a tricyclic antidepressant without sympathomimetic effects, but after 3 weeks this was ineffective. Taking into consideration the patient’s request, an MAOI was reintroduced. Because of the many relapses that followed its withdrawal, iproniazid was once again made available in France. Thus, it was reintroduced gradually under close monitoring of blood pressure. After 6 weeks of treatment, the patient was euthymic. She was instructed to carefully avoid all other vasoactive medications including cold remedies. During the next 6 months, she did not suffer from any recurrent thunderclap headache or any neurological complication.

Figure 1.

Computed tomography cerebral four-vessel. (A and B) Diffuse, multifocal, segmental narrowings (arrows). (C and D) Normalisation 1 month after discharge.

This patient experienced RCVS associated with the intake of a MAOI. The diagnosis of RCVS was established according to the criteria of the International Classification of Headache Disorders on the basis of typical clinical features and a reversible vasoconstriction of cerebral arteries (Headache Classification Committee of the International Headache Society, 2013). Moreover, our patient had not consumed cannabis, and the only precipitating factor was a MAOI prescription. Early diagnosis and prompt treatment produced a good outcome.

The main difficulty was the management of her severe depressive disorder following RCVS. Management of RCVS is primarily based on the identification and elimination of any precipitating or aggravating factors (Calabrese et al., 2007; Ducros, 2012). Finally, it has been recommended that any vasoactive drugs should be stopped and avoided even after the resolution of RCVS due to a potential risk of recurrence. However, in our patient, it was necessary to subsequently rechallenge the MAOI prescription due to the patient’s resistant psychiatric condition and to the failure of alternative options.

In conclusion, psychiatrists should be aware of RCVS, as antidepressants are common triggers. Patients taking selective serotonin-reuptake inhibitors or serotonin–norepinephrine reuptake inhibitors should be advised to seek emergency care in case of unusual severe sudden headache (thunderclap headache). Antidepressants may be carefully re-challenged after RCVS resolution with evidence of normalization of cerebral arteries, weighing the benefits of recovering from a severe depressive episode and the risk of potential recurrence of RCVS.