Mentstrual Psychosis: A forgotten Disorder

Menstrual Psychosis: A Forgotten Disorder?


What Is Menstrual Psychosis?

Menstrual psychosis is a rare and often unrecognized disorder. As the name suggests, this is a particular kind of psychosis that occurs following the menstrual period, usually described as the time frame between 3 days before and 3 days after the first day of the menses.[1-3] In contrast with schizophrenia, menstrual psychosis presents cyclically, full remission is expected between episodes, and the disease does not cause cognitive deterioration.[1] This syndrome gained recognition at the end of the 19th century, with the description of 19 cases by Krafft-Ebing[4] and the later publication of a monograph titled “Psychosis Menstrualis” by the same author.[5] In 1998, Brockington[6] published an extensive review consisting of 275 case studies, showing a cyclic psychosis linked to menstruation. Awareness faded over the years, and today most psychiatrists are unfamiliar with this disorder. However, clinical practice sometimes draws our attention to forgotten diagnoses, bringing them again under the spotlight.

A psychotic patient, a woman in her thirties, walked into the hospital, saying that she was having contractions and was about to deliver. Unable to report her due date, she was asked whether she remembered when she became pregnant. “Yesterday!” she excitedly reported. Two urinary beta HCG tests (pregnancy tests) and an ultrasound ruled out the pregnancy. The patient was lying in bed, face contracted in pain. “I can feel the contractions,” she said and exhaled. Preoccupied, tearful, and confused, she asked to call the father of the baby. He wasn’t surprised at her presentation and commented: “She gets insane around the time of her period.” She confirmed that it was the second day of her period. According to the record, the patient had one previous admission in the same hospital after a psychotic break. The timing was intriguing; she confirmed that it was the second day of her period the last time she was admitted. Unfortunately, the patient refused to answer other questions and was eventually admitted to another facility.

Psychosis and the Menstrual Cycle

There is much literature on the possible correlation between psychotic episodes and the menstrual cycle.[1-3,6] Menstrual psychosis is a fascinating diagnosis with its own phenomenology and treatment. Cyclically, the sufferer will present with episodes of confusion and delirium. These episodes usually cluster around menarche and childbirth, perhaps suggesting a correlation with anovulatory cycles.

The pathophysiology is believed to be increased sensitivity of the dopaminergic receptor during the low estrogen phase. This is supported by the observation that, in schizophrenia, high estrogen levels correlate with low positive symptom scores.[7-9] In other words, estrogen levels appear to be associated with dopamine levels and the “sensitivity” of dopamine D2 receptors. In monkeys, during the follicular (low estrogen) phase, D2 receptors in the striatum have a 12% higher sensitivity than during the luteal (high estrogen) phase.[10] The implication is that in low estrogen periods, higher dopaminergic activity might correlate with the onset of the positive symptoms. This is in line with the dopamine hypothesis of psychosis in which high dopamine levels in the mesolimbic region of the brain have been associated with the onset of positive symptoms.

Possible Neurobiological Mechanism

Estrogens modulate the synthesis of tyrosine hydroxylase in the tuberoinfundibular dopamine (TIDA) system. Tyrosine hydroxylase represents the rate-limiting enzyme for noradrenaline and dopamine production. As Wieck and colleagues[11] suggested, “In TIDA system of normal women, steroid-induced effects may be compensated, leading to no change in post-synaptic dopamine receptor function, whereas in the TIDA system of patients, presynaptic or postsynaptic adaptive mechanisms fail.” In other words, the TIDA system of affected women is unable to compensate for the surge in dopamine induced by the low estrogen phase, perhaps predisposing this population to psychotic outbreak during the menstrual period. Deuchar and Brockington[12] suggest that during anovulatory cycles the brain is exposed to high levels of estrogen that block the D2 receptors. Hypothetically, when the estrogen level drops, exposure of supersensitized D2 receptors to dopamine may trigger a psychotic state.

Pharmacologic Options for Menstrual Psychosis

The suggested neurobiological etiology of menstrual psychosis may point to the use of sex hormones for its treatment. Although antipsychotics can shorten episodes,[13] they have no impact on the cyclic recurrence. Treatment with estrogen, estroprogestinic combinations, or clomiphene could be tried off-label if menstrual psychosis is suspected; these were successfully employed in previous reports.[2,8] Other agents, including selective estrogen receptor modulators[2] and thyroid hormones,[13] have been employed. There is one reported case of a patient suffering from comorbid polycystic ovarian syndrome (PCOS) who benefited from metformin, a medication used for diabetes treatment that leads to restoration of normal menstruation in PCOS.[14]

Estrogens have been studied in the past for augmentation in schizophrenic patients, leading to significant reductions of positive and negative symptoms when delivered as either transdermal or oral preparations.[15,16] Although oral contraceptives may increase blood levels of antipsychotics, perhaps contributing to the reported reduction in symptoms, the transdermal route shows a separate mechanism of action. In reported cases of menstrual psychosis, oral contraceptives prevented cyclic recurrence of symptoms when antipsychotics failed.[17,18] Low-dose birth control pills may be considered a safe initial intervention.[2] Given the correlation with anovulatory cycles, antipsychotics that lead to hyperprolactinemia (typical antipsychotics as well as risperidone and paliperidone) should be avoided in patients with menstrual psychosis

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