Headache Pain, Bipolar Disorder, and Mood Modulators

Case 1:

THE CASE:

A 45-year-old man has a history of migraine that started shortly after puberty. The headaches became more frequent andsevere 3 years ago, when the patient was promoted from metal worker to shift boss.The patient also has a history of depressive episodes, dating back to adolescence, that last from days to weeks. Duringthese episodes, he is apathetic or irritable and timid and spends considerable time sleeping. When he is not depressed, herequires little sleep and is alert and productive.The patient's mother suffered from migraine and depression. His father was an alcoholic who physically and verballyabused the mother, the patient, and his older sister.During the patient's depressed periods, he has sometimes considered suicide. On one occasion, the patient took toomany sleeping pills and had to be hospitalized; however, he denies that this incident was a suicide attempt. He consulted apsychiatrist briefly and occasionally sees a psychotherapist.The patient has missed many days of work because of headache and depression, and he is currently on medicalleave. Recently, agoraphobia has developed, and the patient is afraid to leave his house. He has also become anxiousabout being alone at home when his wife goes to work.The patient self-treats his headaches with marijuana. He also takes opioids and other analgesics, antidepressants,and triptans. Although a triptan can abort his headaches and hydrocodone/acetaminophen and marijuana dull the pain,antidepressants (including selective serotonin reuptake inhibitors, serotonin noradrenaline reuptake inhibitors, tricyclicantidepressants, and monoamine oxidase inhibitors [MAOIs]) are relatively ineffective in preventing the headaches. Thepatient visits the emergency department almost every week for an opioid injection to relieve his headaches. He remainsvery depressed.

• Why are this patient's headaches and depression refractory to antidepressant therapy?
• How would you change the treatment regimen?
• What other interventions might be appropriate for this patient?

Case 1:

THE DIALOGUE:

Primary care doctor:

What's responsible for this patient'spoor response to antidepressants?

Headache specialist:

The poor response is a diagnosticclue that points to a bipolar rather than a unipolar depression.The depression phase of bipolar disorder is somewhatdifferent from depression that is not associated withmood swings. For example, a patient with bipolar disorderis more likely to have symptoms of anxiety and to be lessresponsive to many of the antidepressants.A "mood modulator" is a better choice than an antidepressantfor a patient with bipolar disorder. Some antidepressantscan exacerbate bipolar disorder by elevatinga patient's mood into a manic state. This effect occursmore often with MAOIs and tricyclic antidepressants, butit is also seen with other antidepressants.

Primary care doctor:

What effect will a mood modulatorhave on the patient's headaches?

Headache specialist:

Agents that control mood fluctuationsare becoming increasingly important in the treatment ofchronic pain. For example, lithium is useful in the treatmentof cluster headaches because of the drug's effect onthe hypothalamus. Positron emission tomography scanning has demonstrated the activity of the hypothalamus inboth cluster headaches and manic conditions.The anticonvulsants divalproex, topiramate, carbamazepine,and oxcarbazepine alleviate pain-especiallyneuropathic pain-and are used as mood modulators.Divalproex is indicated for both migraine and bipolarmania.The anticonvulsants I'd recommend for your patientare divalproex or oxcarbazepine. I'd also recommend thathe take a triptan and a nonhabituating analgesic, such asacetaminophen or an NSAID.

Primary care doctor:

How is mania best managed if it occursin this patient?

Headache specialist:

I'd recommend lithium or divalproex.If the mania or hypomania is euphoric, the patient usuallystops complaining about the headache, although the painmay still be present.

Primary care doctor:

The relationship between the headachesand depressive episodes in this patient is unpredictable.The patient sometimes reports fewer headachesbut complains of depression and anxiety. At other times,the headache is the primary complaint.

Headache specialist:

Although the mood may cycle on itsown schedule, it is likely to be influenced by the headachepain. Bipolar disorder and headache seem to exacerbateeach other, and effective treatment of either conditionappears to make the other less intense. It can be difficultto determine which comes first, but I believe that chronicheadache greatly increases the risk of the depressionphase. The more severe the depression, the harder it is tocontrol the chronic daily headaches, which creates anacute situation.In this setting, I would consider adding one of theso-called novel antipsychotics to the regimen. Olanzapine,risperidone, and other drugs in this category can usuallycontrol or modify mania or hypomanic symptoms in a fewdays. If the patient has been taking divalproex, measurethe blood valproic acid level to determine whether it is inthe therapeutic range. The clinical scenario can becomequite complicated, and hospitalization may be warranted.

Primary care doctor:

I have prescribed diazepam andlorazepam to treat the patient's anxiety, and zolpidem topromote sleep. Would you recommend any changesto this regimen?

Headache specialist:

Anxiety and sleep disorders are notunusual in patients with bipolar disease. A study of comor-bidity of anxiety and depression concluded that patientswith long-term depression also have some anxiety.

¹

About93% of patients with bipolar spectrum disorder also havesymptoms of an anxiety disorder. There is no consensusabout the treatment of comorbid anxiety, but medicationsthat enhance the action of Υ-aminobutyric acid (GABA)can be used. Many of the mood modulators are also"GABA-ergic" drugs. I frequently prescribe combinationtherapy for patients.

Primary care doctor:

The narcotizing effect of marijuanasufficiently relieves the patient's pain to permit him tocontinue functioning for a period. However, I'm concernedthat marijuana dependency has enveloped him in a lethargichaze that prevents him from seeking more effectivetreatments, changing his lifestyle, or finding solutions tohis problems.

Headache specialist:

Your concern is well-founded. Marijuanadoes not cure or prevent pain; it has only abortiveand soporific effects.Detoxification and cessation of marijuana use are indicated.If the patient is hospitalized, marijuana use canbe stopped and the other conditions can be treated appropriatelywhile withdrawal symptoms are managed. If thepatient prefers outpatient treatment, refer him to an addictionspecialist.If this patient's headaches continue to be refractoryto treatment after detoxification from marijuana, it may behelpful to determine whether the bipolar disorder is stabilized,cycling is controlled, and mood disorder symptomshave resolved. Consultation with a psychiatrist and a psychopharmacologistwould be helpful.

Primary care doctor:

Are chronic headaches and moodswings closely linked even in patients who do not havebipolar disorder?

Headache specialist:

It's clear that constant pain and disabilityare discouraging and thus provoke a pessimistic,anxious outlook. It's slightly less clear why or how depressionaffects pain. Fordyce

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studied the behavior of personswith chronic pain and found that depressed patientsexperienced pain sensations more acutely and had lessability to filter out or distract themselves from these sensations.Of course, depressed persons have less endorphinsecretion than non-depressed persons. Research suggeststhat serotonin and norepinephrine pathways travel toboth pain centers and depression centers in the cerebralcortex.

³

Case 2:

FOCUS ON CHRONIC HEADACHE AND BIPOLAR DISORDER

How is chronic headache best treated in a patient with bipolar disorder?

Case 2:

A "mood modulator" is a better choice than an antidepressant for a patient with bipolar disorder. Agents used tocontrol mood fluctuations-such as the anticonvulsants divalproex, topiramate, carbamazepine, and oxcarbazepine-can also alleviate pain. Antidepressants are less likely to be effective in patients with bipolar disorder, and some-especiallymonoamine oxidase inhibitors and tricyclic antidepressants-can precipitate a manic state.

Case 3:

FOCUS ON CHRONIC HEADACHE AND BIPOLAR DISORDER

What are the treatment options for comorbid anxiety in a patient with bipolar disorder?

Case 3:

There is no consensus about the treatment of comorbid anxiety, but medications that enhance the action ofΥ-aminobutyric acid (GABA) can be used. Many of the mood modulators are also "GABA-ergic" drugs.

Case 4:

FOCUS ON CHRONIC HEADACHE AND BIPOLAR DISORDER

How is a manic crisis best managed in a patient with chronic headache and bipolar disorder?

Case 4:

Consider adding one of the so-called novel antipsychotics, such as olanzapine or risperidone, to the regimen.These antipsychotics can usually control or modify mania or hypomanic symptoms in a few days. If the patient hasbeen taking divalproex, measure the blood valproic acid level to determine whether it is in the therapeutic range.Hospitalization may be warranted.

References:

REFERENCES:

1.

Diamond S. Depression and headache.

Headache.

1983;23:122-126.

2.

Fordyce WE. Behavioral concepts in chronic pain and illness. In: DavidsonPO, ed.

The Behavioral Management of Anxiety, Depression, and Pain.

New York:Brunner/Mazel; 1976:147-174.

3.

Breslau N, Schultz LR, Stewart WF, et al. Headache and major depression: isthe association specific to migraine?

Neurology.

2000;54:308-313.