Consultation request

You are being consulted by a neurologist as a psychiatrist to assess the patient psychiatrically and support further treatment planning.

Current history

This concerns a 26-year-old patient who has been neurologically treated since the age of 18 for increasing episodic headaches and shortening symptom-free intervals.

The headaches were described as unilateral and pulsating. Because of accompanying symptoms such as nausea and light sensitivity and an attack duration of half a day up to two to three days, migraine without aura was diagnosed.

Previous therapy

Initially the patient received sumatriptan 10 mg as a nasal spray for acute therapy as needed. Due to an attack frequency of about two migraine attacks per week, prophylaxis with amitriptyline at a dose of 150 mg daily was subsequently initiated.

Under this treatment there was a marked improvement in the headaches, so that according to the patient she was able to manage her normal everyday life again for about six months.

Onset of anxiety symptoms

Subsequently, however, panic attacks occurred. During this time she suffered from sleep disturbances and irritability and reported sudden episodes of anxiety without an identifiable trigger, with a frequency similar to that of the migraine attacks.

In the further course amitriptyline was replaced by propranolol 60 mg daily for migraine prophylaxis. Under this the panic attacks decreased, and the patient reported a partial improvement lasting several months.

Recurrent deterioration

After several months of relative stabilization the patient experienced, according to her report, “one of the worst headaches of her life” which lasted about an hour. On the same day a pronounced panic attack and a marked psychological deterioration occurred. In the emergency department a physical examination and a cranial computed tomography were performed, both without pathological findings.

Further course

In the further course prophylaxis with botulinum toxin was initiated. In the following two years migraine attacks occurred only about twice per season. Occasional panic attacks persisted.

During this period the patient also developed a depressive episode of about two months’ duration, accompanied by marked anxiety, inner restlessness, insomnia, increased activity and irritability or aggressive behavior. In her own assessment there was an association with the autumn season.

Family history

Family history: the patient reports that her mother suffered from postpartum depression and one of her aunts repeatedly attempted suicide.

Current question

Most recently the treating neurologist initiated a trial of venlafaxine, under which both the headaches and the anxiety symptoms worsened.

A psychiatric consultation and support with further appropriate treatment are now requested.

Discussion of the case in the online conference

The case will be presented in the weekly online conference for the discussion of consultation cases.

Indication for migraine prophylaxis

Dr. Diaz explains that the indication for pharmacological migraine prophylaxis in this case is clearly given, since the patient has suffered repeated migraine attacks since adolescence that significantly impair her daily functioning.

Psychiatric classification

Particularly relevant, however, is the simultaneous depressive and anxious symptomatology. Because of the course of the depressive episodes, the early onset of illness, the reported irritability and overactivity and the positive family history, an affective disorder must be considered, most likely within the bipolar spectrum.

The panic attacks are regarded rather as a concomitant symptom that temporarily intensifies in the context of a relapse of the affective disorder or the migraine. There is, however, insufficient evidence for the diagnosis of an independent anxiety disorder as the primary illness.

Thus a combination of migraine and an affective disorder—most likely a bipolar II disorder—is probably present. In the context of relapses of both conditions there is an increase in anxiety symptoms, while the panic attacks occur only occasionally during the symptom-free interval and do not significantly impair daily life.

Assessment of previous therapy

The patient benefited from amitriptyline only temporarily. The recurrence of symptoms could indicate the onset of a new affective episode, with the tricyclic antidepressant possibly contributing to mood instability in an individual with corresponding vulnerability.

Although amitriptyline is among the preferred first-line medications for migraine prophylaxis, a different first-line drug was therefore chosen and therapy with valproate was initiated.

Therapy with valproate

Valproate at a dose of 750 to 2000 mg daily is not only effective for migraine prophylaxis but is also approved as maintenance therapy for bipolar disorders.

Especially with accompanying anxiety symptoms or comorbid panic disorder it is considered a suitable treatment option and therefore represents a reasonable choice for this patient.

Other treatment options

Beta blockers, venlafaxine and topiramate also belong to the drugs that can be used for migraine prophylaxis.

However, propranolol shows only limited effect on most anxiety disorders and can worsen depressive symptoms in some patients.

Venlafaxine, in turn, has a pronounced serotonergic effect and carries the risk in this patient of triggering a manic episode or worsening the anxiety symptoms.

Special situation: additional epilepsy

In the further course of the conference the question is discussed how the therapeutic approach would change if epilepsy were also present.

In that case there would be an additional reason to prescribe valproate. Depending on the seizure type, valproate is an effective therapy option for both focal seizures and generalized or absence seizures.

Dosage and therapeutic serum level

The therapeutic serum level for the treatment of epilepsy and affective disorders lies in a similar range of about 45 to 125 µg/ml.

This is generally achieved with doses between 750 mg and 2 g daily, depending on the patient.

Since a stable active level is reached after approximately five days, treatment can be started with 250 mg and increased after five days to 750 mg daily. A renewed clinical assessment should then take place.

Pregnancy and breastfeeding

With a desire for children or planned pregnancy valproate should be avoided if possible.

In such a case lamotrigine could be an alternative, as it is considered comparatively safe in pregnancy.

Valproate increases the risk of fetal neurological malformations due to its effect on neural tube development by about 4–5% and is also associated with an increased risk of cognitive developmental disorders and autism in the child.

Therefore, in women of childbearing potential an additional administration of 1 mg folic acid daily is generally recommended.

During breastfeeding, however, valproate is considered safe and is preferably used.

Side effects and safety aspects

The most common side effect at the beginning of treatment is nausea, which usually subsides over time.

In addition, up to 40% of patients may experience a transient increase in liver values to less than three times the normal value, which usually has no consequences if the clinical condition is stable.

Fatal liver failure is very rare and occurs in about one in 40,000 patients.

FDA black box warning: In older patients there is an increased risk of sedation and falls, so therapy should be initiated particularly cautiously.

Summary

Area	Key terms
Demographics	26-year-old patient
Migraine history	Migraine without aura, since age 18, increasing attack frequency, shortening symptom-free intervals
Headache character	Unilateral, pulsating, duration ½ to 2–3 days
Associated migraine symptoms	Nausea, light sensitivity (photophobia)
Acute therapy	Sumatriptan 10 mg nasal spray as needed
Migraine prophylaxis I	Amitriptyline 150 mg daily
Course under amitriptyline	Marked improvement of headaches, return to normal daily life for about 6 months
Anxiety symptomatology	Panic attacks, sudden episodes of anxiety without identifiable trigger, frequency similar to migraine attacks
Other symptoms	Sleep disturbances, irritability
Migraine prophylaxis II	Propranolol 60 mg daily
Course under propranolol	Reduction of panic attacks, partial improvement lasting months
Acute deterioration	“One of the worst headaches of her life,” duration about 1 hour
Accompanying psychological symptoms	Severe panic attack, marked psychological deterioration
Emergency diagnostics	Physical examination unremarkable, cranial CT without pathological findings
Migraine prophylaxis III	Botulinum toxin
Further course	Migraine attacks only about twice per season, occasional panic attacks
Depressive episode	Duration about 2 months
Affective episode	Anxiety, inner restlessness, insomnia, increased activity, irritability, aggressive behavior
Special feature	Association with the autumn season
Family history	Mother with postpartum depression, an aunt with repeated suicide attempts
Other medication	Venlafaxine
Course under venlafaxine	Worsening of headaches and increase in anxiety symptoms
Psychiatric differential diagnoses	Panic disorder, bipolar disorder, bipolar II disorder, mixed episode, recurrent depressive disorder
Exam-relevant notes	Positive family history, activation under antidepressants, comorbidity of migraine and affective disorders, consultation psychiatry, therapy planning in comorbid migraine and affective disorder