Headache and Mood Swings — Interdisciplinary

You work as a psychiatrist in a hospital and are consulted by a neurologist to assess a patient and assist with medication selection. The patient presented to him this morning.

The case concerns a 26-year-old woman who has been under neurological care since about the age of 18 after her recurrent headaches intensified and the intervals between attacks progressively shortened.

The headaches are predominantly unilateral and pulsating. Nausea and light sensitivity occur as accompanying symptoms. A single attack lasts between half a day and two to three days.

The patient is awake and fully oriented. Blood pressure 118/76 mmHg, pulse 78/min, temperature 36.7 °C. No meningism. Cranial nerves, motor function, sensation, reflexes and coordination are unremarkable. The previous headaches had developed gradually; currently there is no change in the usual pain character.

Due to these complaints, a diagnosis of migraine was made. For acute treatment the patient received sumatriptan. Because the headaches occurred about twice weekly, prophylaxis with 150 mg amitriptyline was initiated.

The patient reports that her headaches actually decreased significantly under this treatment. For about six months she was able to live a normal life again. Subsequently panic attacks occurred.

During this period she also describes sleep disturbances and irritability. The panic attacks occurred unexpectedly and without an identifiable trigger, approximately as frequently as the migraine attacks had been at their worst phase.

Thereupon amitriptyline for migraine prophylaxis was replaced by propranolol at a dose of 60 mg daily. The panic attacks diminished. After some months with partial improvement, however, she experienced what she described as “one of the worst headaches of my life” for an hour. On the same day she also had a severe panic attack. She also recalls that she felt markedly worse psychologically.

Finally she received botulinum toxin for migraine prophylaxis. Under this treatment the migraine attacks occurred only about twice per quarter over a period of two years. Occasional panic attacks persisted.

In this phase she experienced a pronounced depressive episode lasting two months. This was accompanied by anxiety, inner restlessness, insomnia, increased activity and aggressive behavior. The patient herself also saw a seasonal connection, as the episode occurred in autumn.

Her mother had suffered from depression after a childbirth. One of her maternal aunts had repeatedly attempted suicide.

The neurologist initiated treatment with 150 mg venlafaxine. Under this medication the headaches worsened and the anxiety increased.

Now support is requested for further treatment.

The case is presented in a weekly online meeting of psychiatric consultation cases. Dr. Diaz explains:

“There is no doubt about the necessity of pharmacological migraine prophylaxis. The patient has experienced monthly migraine attacks since her youth that have impaired her daily life.

However, the simultaneous occurrence of depressive symptoms and anxiety symptoms is decisive. Given the course of the depressive episodes, the age of onset, the accompanying aggressiveness and increased activity as well as the positive family history, the suspicion of an affective disorder is near, which with high probability belongs to the bipolar spectrum.”

Dr. Diaz continues:

“Regarding the panic attacks, we also think more of anxiety episodes as a concomitant symptom that temporarily intensify when an affective episode recurs or when the migraine worsens. Apparently the full criteria for a primary anxiety disorder as the leading diagnosis are not met.

Thus we are dealing with a patient who suffers from migraine and an affective disorder, with findings that speak for bipolar II disorder. When either of these two conditions worsens, the panic attacks also increase. Outside of these phases they occur only occasionally and do not significantly impair her daily life.

The patient benefited only temporarily from amitriptyline. The renewed symptom increase could, according to her account, indicate the onset of another affective episode. In that case the tricyclic antidepressant could, given her individual predisposition, have contributed to mood destabilization. Although amitriptyline is among the preferred first-line drugs for migraine prophylaxis, we therefore chose another first-line agent and prescribed valproate.

Sodium valproate in an appropriate dosage of 750 to 2,000 mg is effective not only for migraine prophylaxis but is also approved as a maintenance medication for bipolar-spectrum disorders. It is considered a drug of choice especially when accompanying anxiety symptoms or comorbid panic disorder are present. Therefore it represents a suitable option for this patient.

Beta blockers and venlafaxine, alongside topiramate, are among other medications used for migraine prophylaxis. However, propranolol has only limited effect on many anxiety symptoms and may possibly induce depressive complaints in some people. In this patient it did not achieve the desired effect.

With venlafaxine there is a risk, due to its relatively pronounced serotonergic action, of triggering mania in this patient. It can also increase anxiety.”

In the further discussion one of the junior doctors asks whether the approach would change if the patient additionally suffered from an epileptic seizure disorder. They also discuss what significance a planned pregnancy would have for medication choice.

Dr. Diaz explains:

“If an additional seizure disorder were present, we would have another reason to use valproate. However, it depends on the seizure type. In focal seizures the drug is one of our first-line agents. It is also effective in generalized seizures and even in absence seizures.

The effective serum level for treating seizures and affective disorders lies in a similar range, namely between 45 and 125 µg/ml. This level is reached depending on the patient with a daily dose between 750 mg and 2 g. Because it takes about five days to achieve a stable level, treatment can be started with 250 mg and the daily dose increased to 750 mg after five days. A reassessment then follows.

If a pregnancy is planned, we avoid valproate whenever possible. In that case one could consider, for example, lamotrigine, as it is regarded as largely safe in pregnancy. Valproate can cause neural tube defects in the unborn child with a probability of about 4 to 5 % due to its effects on the neural tube. In addition, it increases the risk of cognitive developmental disorders and autism. When prescribing to women of childbearing potential it is generally recommended to give an additional 1 mg of folic acid daily. During breastfeeding the drug is considered safe and is preferred.

The most common side effect at the start of treatment is nausea, which decreases over time.

In up to 40 % of treated patients there can be a temporary increase in liver enzymes to less than three times the upper normal limit. As long as the patient remains clinically stable, this is not of major significance.

Fatal liver failure is rare and may occur in about one in 40,000 treated individuals.”

FDA “black box” warning: risk of sedation and falls in elderly people; therefore particularly cautious initiation of treatment is recommended.