AMERICAN ACADEMY OF CHILD & ADOLESCENT PSYCHIATRY – BIPOLAR DISORDER RESOURCE CENTER
Are there any medications I should avoid if I have bipolar disorder?
The medications you should be concerned about can be divided into two broad categories-those that may directly provoke or exacerbate mania and those that interact negatively with medications used to treat bipolar disorder. In addition to prescription medication, there are over-the-counter medications, street drugs, and herbal remedies that should be avoided and are thus being lumped into the category of “medications” here.
Medications that provoke or exacerbate mania can be divided into four subcategories:
• Antidepressants and stimulants used commonly to treat psychiatric and neurological conditions
• Steroids and beta agonists used commonly to treat pulmonary conditions
• Dopamine agonists used commonly to treat neurological conditions
• Over-the-counter medications and street drugs that are stimulants and hallucinogens
Antidepressants cause the most concern among patients and clinicians alike for two main reasons: they may cause switching to mania and/or they may cause mood to destabilize, leading to worsening depression.
Two recent reviews have focused on the issue of switching from depression into mania. In the first study reviewing a very complex literature on the subject using very sophisticated statistics, the switch rate appeared to be between 20% to 40%, with tricyclic antidepressants causing higher rates than SSRIs. The study also suggested that being on a mood stabilizer provided only partial protection against switching. In another study, however, which looked only at randomized trial data, switch rates on antidepressants were no different than placebo in the short run. Most agree that switching can definitely occur in patients with bipolar I disorder. The greatest controversy lies in how to properly treat patients with bipolar spectrum disorders, as the vast majority of them are predominantly depressed. Patients who are seen in a bipolar specialty clinic in a tertiary care center are less likely to be prescribed an antidepressant than if they saw a community psychiatrist. This may be due to the fact that most patients who are sent to a tertiary care center have already failed multiple medication trials, including antidepressants. In fact, it appears that one of the indicators of switching is a past history of failed multiple antidepressant trials. Finally, to complicate matters more, the abrupt withdrawal of antidepressant medications can cause a manic switch, so a slow taper is strongly advised for bipolar patients on them.
With respect to mood destabilization, or an increase in cycle frequency, the available literature seems to support the concept that the addition of antidepressants can cause patients to cycle much more often than if they were not on an antidepressant. Furthermore, bipolar disorder often worsens over the years through a process that may be identical to kindling. Antidepressants may hasten the process, although there is no literature currently to support that. Unfortunately, no randomized studies have been performed, so the available literature is scant. Because studies have demonstrated reduced suicidality with patients on either Depakote (valproate) or lithium and no clear benefits with respect to suicidality with bipolar patients on antidepressants, most doctors feel strongly that treating depression with mood stabilizers that have antidepressant effects (lithium and Lamictal [lamotrigine]) should be the first course of action in bipolar patients, and if antidepressants are necessary they should be discontinued as soon as the depression has resolved.
A long history of research demonstrates a link between hormonal levels and mood disorders. Hormones are chemicals produced by endocrine glands that are released into the blood stream to carry out functions in other parts of the body. Hormone-producing endocrine glands include the thyroid, which produces thyroid hormone; the adrenal glands, which produce adrenaline or epinephrine, among others; and the reproductive glands, which produce testosterone and estrogen, among others. Hormones clearly play a role in various mood disorders such as premenstrual dysphoric disorder, postpartum depression, major depression, and bipolar disorder. Recently the issue of steroid use among professional athletes has been discussed in the press, as there have been a number of cases of suicides in previously mentally healthy young men who used them as performance enhancers. Steroids are often used to treat a variety of medical conditions that cause inflammation as they reduce the inflammatory process. But steroids are extremely activating, causing the body to mobilize into the “fight or flight” mode. The body also generates this mode naturally when very stressful circumstances occur. It is caused by a part of the involuntary, or autonomic, nervous system known as the sympathetic nervous system. Its counterpoint, which causes “rest or restoration,” is known as the parasympathetic nervous system. These systems act on both the body and the brain. The sympathetic system uses the chemical norepinephrine (noradrenalin), which is similar to epinephrine (adrenalin). Epinephrine is often given to people who have severe allergies to bee stings, foods, or medications. These allergic reactions cause a condition known as anaphylaxis, which can cause such severe swelling in the pharynx, making it impossible to breathe. Epinephrine is life saving in such circumstances. But the consequences are that the system is activated. For those with mood disorders, particularly bipolar disorder, this can have a destabilizing effect and cause relapse. Any medication that activates the sympathetic nervous system can do this, not just steroids. Medications used to treat asthma, emphysema, chronic bronchitis, or other pulmonary conditions that cause wheezing stimulate the sympathetic system to make the airways bigger in order to breathe easier. These medications are known as beta-agonists as they stimulate beta-receptors of the sympathetic nervous system, causing the airways to dilate. Such stimulation, however, affects the sympathetic nervous system throughout the body in addition to the airways. There are also over-the-counter medications that can have a similar effect. Prior to removal from the market, Ephedra was known for this effect, but any medication that contains phenylpropanolamine has that potential. Stimulants, too, can potentially do this. The final com-mon pathway of all these medications, including antidepressants, appears to be their impact on norepinephrine, of which TCAs have more of an impact than SSRIs. But this includes street drugs that have stimulant properties or hallucinogenic properties (uppers and hallucinogens). Downers, on the other hand, which include barbiturates and alcohol, can destabilize mood due to their withdrawal effects, which mimic a sympathetic response. This is one of the reasons why it is critical to avoid alcohol and drugs of abuse. Finally, because of the popularity of recent herbal remedies, we have listed various herbs with psychotropic effects, with their adverse effects and interactions. These herbs should be avoided by all individuals with mood disorders.
Are there any medical conditions that can cause mania or depression?
Medical conditions should always be considered as a potential cause or exacerbating source for a manic or depressive episode. Because of their medical background, psychiatrists routinely consider medical conditions as possible causes for mood disorders and thus will assess a person’s medical history. Your psychiatrist may consider obtaining laboratory tests as part of screening for medical conditions, or he or she may defer this evaluation to your primary care physician. Most often, mania and depression occur independently of another medical disorder, but if there are physical signs and symptoms other than those typically found in a mood disorder, a medical/physical examination to rule out physical causes for the mood symptoms is warranted. Also, if a medical condition exists, it may very well be that the mood symptoms are not physiologically related but merely co-occurring with the illness.
Endocrine disorders, cardiac conditions, cancers, neurological conditions, vitamin deficiencies, autoimmune disorders, and so on can be associated with depression or mania. Treatment of the co-occurring medical disorder may not result in resolution of the mood symptoms, but their resolution would support the physiological connection. Even so, for chronic medical conditions, long-term treatment may still be required with antidepressant or antimanic medications.
So-called secondary mania can occur from brain-based disorders, such as head injury, stroke, tumors, and migraines. Bipolar disorder is more common in patients with multiple sclerosis than in the general population. Infections that may result in mania include HIV, Lyme disease, and neurosyphilis.
Medical causes of depression and mania
Medical Causes of Depression
Endocrine: hypothyroid, Cushing’s disease, Addison’s disease, diabetes
Infection: AIDS, Lyme disease, hepatitis
Cancer: pancreatic, occult, brain
Neurological: dementia, Parkinson’s disease, stroke
Cardiac: coronary artery disease, heart failure, heart attack
Medications: antihypertensives, steroids, oral contraceptives
Medical Causes of Mania
Endocrine: hyperthyroid, Cushing’s disease
Infection: AIDS, encephalitis, syphilis
Autoimmune: lupus
Neurological: multiple sclerosis, dementia, stroke, temporal lobe epilepsy
Medications: antidepressants, steroids, amphetamines, L-dopa
My aging father has always been an energetic individual but has never suffered from a mental illness. Recently he became manic for the first time in his life and ended up in the hospital. I had never heard of someone developing bipolar disorder in late life. Is that possible?
It is possible to develop bipolar disorder in late life. But it is important to distinguish between two types of mania in the geriatric population, primary mania and secondary mania. Primary mania is called bipolar disorder. Secondary mania is due to an underlying toxic or metabolic condition. About 10% of all patients with bipolar disorder have their first manic episode after the age of 50. However, both primary and secondary manias have a prevalence of less than 1% in the general geriatric population. In contrast to their younger peers, geriatric mania is usually associated with mixed manic and depressive symptoms and often associated with sleep disturbance, mood-incongruent paranoid delusions, cognitive impairments, and irritability more than hyperactivity. Additionally, increased goal-directed activities with a high degree of negative consequences are less prominent than in the younger population.
Distinguishing primary from secondary mania is of critical importance in this population, because underlying medical conditions associated with secondary mania often lead to delirium that comes with high mortality rates if the underlying medical condition is not corrected. Delirium is known also as an acute confusional state and is associated with a waxing and wan-ing of consciousness. Nighttime agitation and confusion, also known as “sun-downing,” is more typically associated with delirium than primary mania. Neurological disorders are associated with about 75% of cases of secondary mania. These include encephalitis, other brain infections, vascular diseases, tumors, and dementias.
One must never leave out the prospect that the mania was medication induced. The geriatric population is particularly susceptible to medication side effects, and many medications can cause delirium and psychosis.
Such medications include:
• Sedative/hypnotics (also alcohol)
• Anticholinergics (including Parkinson’s disease medications and bladder control medications)
• Opiates (including Dilaudid or Fentanyl)
• Sympathomimetics (including decongestants, bronchodilators, and steroids)
The treatment for mania is symptom control, and therefore many of the treatments for primary and secondary mania are similar. Whenever a patient over the age of 50 with no prior history of mental illness presents with symptoms of mania, however, a thorough medical evaluation is indicated because the likelihood of an underlying medical condition causing the psychiatric symptoms increases dramatically with age. Thus the question of psychiatric treatment for primary verses secondary mania varies little in the acute phase of the illness. In the long run, however, patients with primary bipolar disorder will need to be maintained on their medication while those with secondary mania should be able to come off their psychiatric medications once the underlying medical condition is corrected.
Terms:
Endocrine glands – ductless glands in the body that synthesize and secrete chemical messengers (hormones) into the blood stream or lymph for transport to target cells.
Sympathetic nervous system – the part of the autonomic nervous system that is responsible for providing responses and energy needed to cope with stressful situations such as fear or extremes of physical activity.
Parasympathetic nervous system – that part of the autonomic nervous system that allows for rest, recovery, and storage of new energy in the body between stressful situations.
Endocrine disorder – a disorder of the endocrine system.
Endocrine glands – release chemicals (also known as hormones), whose actions occur at another site, directly into the blood stream
Delirium – a temporary state of mental confusion resulting from high fever, intoxication, shock, or other causes, and characterized by anxiety, disorientation, memory impairment, hallucinations, trembling, and incoherent speech.
