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Lithium salts are chemical salts of lithium used primarily in the treatment of bipolar disorder as mood stabilizing drugs. They are also sometimes used to treat depression and mania. more...
Lithium carbonate (Li2CO3), sold as Carbolith®, Cibalith-S®, Duralith®, Eskalith®, Lithane®, Lithizine®, Lithobid®, Lithonate® and Lithotabs®, is the most commonly prescribed, whilst the citrate salt lithium citrate (Li3C6H5O7), the sulfate salt lithium sulfate (Li2SO4), the oxybutyrate salt lithium oxybutyrate (C4H9LiO3) and the orotate salt lithium orotate are alternatives.
Lithium is widely distributed in the central nervous system and interacts with a number of neurotransmitters and receptors, decreasing noradrenaline release and increasing serotonin synthesis.
The use of lithium salts to treat mania was first proposed by the Australian psychiatrist John Cade in 1949, after he discovered the effect of first lithium urate, and then other lithium salts, on animals. Cade soon succeeded in controlling mania in chronically hospitalized patients. This was the first successful application of a drug to treat mental illness, and opened the door for the development of medicines for other mental [[problems in the next decades.
The rest of the world was slow to adopt this revolutionary treatment, largely because of deaths which resulted from even relatively minor overdosing, and from use of lithium chloride as a substitute for table salt. Largely through the research and other efforts of Denmark's Mogens Schou in Europe, and Samuel Gershon in the U.S., this resistance was slowly overcome. The application of lithium for manic illness was approved by the United States Food and Drug Administration in 1970.
Lithium treatment is used to treat mania in bipolar disorder. Initially, lithium is often used in conjunction with antipsychotic drugs as it can take up to a week for lithium to have an effect. Lithium is also used as prophylaxis for depression and mania in bipolar disorder. Also, it is sometimes used for other disorders, like cycloid psychosis, unipolar depression, migraine and others. It is sometimes used as an "augmenting" agent, to increase the benefits of standard drugs used for unipolar depression. Lithium treatment is generally considered to be unsuitable for children.
Mechanism of Action
The precise mechanism of action of Li+ as a mood-stabilizing agent is currently unknown, but it is possible that Li+ produces its effects by interacting with the transport of monovalent or divalent cations in neurons. However, because it is a poor substrate at the sodium pump, it cannot maintain a membrane potential and only sustains a small gradient across biological membranes. Yet Li+ is similar enough to Na+ in that under experimental conditions, Li+ can replace Na+ for production of a single in neurons. Perhaps most the most interesting characteristic of Li+, is that it produces no obvious psychotropic effects (such as sedation, depression, euphoria) in normal individuals at therapeutic concentrations, differentiating it from the other psychoactive drugs.
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From Gale Encyclopedia of Medicine,
by Paula Anne Ford-Martin
Bipolar, or manic-depressive disorder, is a mood disorder that causes radical emotional changes and mood swings, from manic highs to depressive lows. The majority of bipolar individuals experience alternating episodes of mania and depression.
In the United States alone, bipolar disorder afflicts almost two million people at an annual cost of over $45 billion, according to a 1991 report by the National Institutes of Mental Health. The average age of onset of bipolar disorder is from adolescence through the early twenties. However, because of the complexity of the disorder, a correct diagnosis can be delayed for several years or more. In a survey of bipolar patients conducted by the National Depressive and Manic Depressive Association (MDMDA), one-half of respondents reported visiting three or more professionals before receiving a correct diagnosis, and over one-third reported a wait of ten years or more before they were correctly diagnosed.
The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), the diagnostic standard for mental health professionals in the United States, defines four separate categories of bipolar disorder: bipolar I, bipolar II, cyclothymia, and bipolar not-otherwise-specified (NOS).
Bipolar I disorder is characterized by manic episodes, the "high" of the manic-depressive cycle. A bipolar patient experiencing mania often has feelings of self-importance, elation, talkativeness, increased sociability, and a desire to embark on goal-oriented activities, coupled with the characteristics of irritability, impatience, impulsiveness, hyperactivity, and a decreased need for sleep. Usually this manic period is followed by a period of depression, although a few bipolar I individuals may not experience a major depressive episode. Mixed states, where both manic or hypomanic symptoms and depressive symptoms occur at the same time, also occur frequently with bipolar I patients (for example, depression with the racing thoughts of mania). Also, dysphoric mania is common (mania characterized by anger and irritability).
Bipolar II disorder is characterized by major depressive episodes alternating with episodes of hypomania, a milder form of mania. Bipolar depression may be difficult to distinguish from a unipolar major depressive episode. Patients with bipolar depression tend to have extremely low energy, retarded mental and physical processes, and more profound fatigue (for example, hypersomnia; a sleep disorder marked by a need for excessive sleep or sleepiness when awake) than unipolar depressives.
Cyclothymia refers to the cycling of hypomanic episodes with depression that does not reach major depressive proportions. A third of patients with cyclothymia will develop bipolar I or II disorder later in life.
A phenomenon known as rapid cycling occurs in up to 20% of bipolar I and II patients. In rapid cycling, manic and depressive episodes must alternate frequently; at least 4 times in 12 months; to meet the diagnostic definition. In some cases of "ultra-rapid cycling," the patient may bounce between manic and depressive states several times within a 24-hour period. This condition is very hard to distinguish from mixed states.
Bipolar NOS is a category for bipolar states that do not clearly fit into the bipolar I, II, or cyclothymia diagnoses.
Causes & symptoms
The source of bipolar disorder has not been clearly defined. Because two-thirds of bipolar patients have a family history of affective or emotional disorders, researchers have searched for a genetic link to the disorder. Several studies have uncovered a number of possible genetic connections to the predisposition for bipolar disorder. Another possible biological cause under investigation is the presence of an excessive calcium build-up in the cells of bipolar patients. Also, dopamine and other neurochemical transmitters appear to be implicated in bipolar disorder and these are under intense investigation.
Over half of patients diagnosed with bipolar disorder have a history of substance abuse. There is a high rate of association between cocaine abuse and bipolar disorder. Some studies have shown up to 30% of abusers meeting the criteria for bipolar disorder. The emotional and physical highs and lows of cocaine use correspond to the manic depression of the bipolar patient, making the disorder difficult to diagnosis.
For some bipolar patients, manic and depressive episodes coincide with seasonal changes. Depressive episodes are typical during winter and fall, and manic episodes are more probable in the spring and summer months.
Symptoms of bipolar depressive episodes include low energy levels, feelings of despair, difficulty concentrating, extreme fatigue, and psychomotor retardation (slowed mental and physical capabilities). Manic episodes are characterized by feelings of euphoria, lack of inhibitions, racing thoughts, diminished need for sleep, talkativeness, risk taking, and irritability. In extreme cases, mania can induce hallucinations and other psychotic symptoms such as grandiose illusions.
Bipolar disorder is usually diagnosed and treated by a psychiatrist and/or a psychologist with medical assistance. In addition to an interview, several clinical inventories or scales may be used to assess the patient's mental status and determine the presence of bipolar symptoms. These include the Millon Clinical Multiaxial Inventory III (MCMI-III), Minnesota Multiphasic Personality Inventory II (MMPI-2), the Internal State Scale (ISS), the Self-Report Manic Inventory (SRMI), and the Young Mania Rating Scale (YMRS). The tests are verbal and/or written and are administered in both hospital and outpatient settings.
Psychologists and psychiatrists typically use the criteria listed in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) as a guideline for diagnosis of bipolar disorder and other mental illnesses. DSM-IV describes a manic episode as an abnormally elevated or irritable mood lasting a period of at least one week that is distinguished by at least three of the mania symptoms: inflated self-esteem, decreased need for sleep, talkativeness, racing thoughts, distractibility, increase in goal-directed activity, or excessive involvement in pleasurable activities that have a high potential for painful consequences. If the mood of the patient is irritable and not elevated, four of the symptoms are required.
Although many clinicians find the criteria too rigid, a hypomanic diagnosis requires a duration of at least four days with at least three of the symptoms indicated for manic episodes (four if mood is irritable and not elevated). DSM-IV notes that unlike manic episodes, hypomanic episodes do not cause a marked impairment in social or occupational functioning, do not require hospitalization, and do not have psychotic features. In addition, because hypomanic episodes are characterized by high energy and goal directed activities and often result in a positive outcome, or are perceived in a positive manner by the patient, bipolar II disorder can go undiagnosed.
Bipolar symptoms often present differently in children and adolescents. Manic episodes in these age groups are typically characterized by more psychotic features than in adults, which may lead to a misdiagnosis of schizophrenia. Children and adolescents also tend toward irritability and aggressiveness instead of elation. Further, symptoms tend to be chronic, or ongoing, rather than acute, or episodic. Bipolar children are easily distracted, impulsive, and hyperactive, which can lead to a misdiagnosis of attention deficit hyperactivity disorder (ADHD). Furthermore, their aggression often leads to violence, which may be misdiagnosed as a conduct disorder.
Substance abuse, thyroid disease, and use of prescription or over-the-counter medication can mask or mimic the presence of bipolar disorder. In cases of substance abuse, the patient must ordinarily undergo a period of detoxification and abstinence before a mood disorder is diagnosed and treatment begins.
Treatment of bipolar disorder is usually by means of medication. A combination of mood stabilizing agents with antidepressants, antipsychotics, and anticonvulsants is used to regulate manic and depressive episodes.
Mood stabilizing agents such as lithium, carbamazepine, and valproate are prescribed to regulate the manic highs and lows of bipolar disorder:
- Lithium (Cibalith-S, Eskalith, Lithane, Lithobid, Lithonate, Lithotabs) is one of the oldest and most frequently prescribed drugs available for the treatment of bipolar mania and depression. Because the drug takes four to ten days to reach a therapeutic level in the bloodstream, it is sometimes prescribed in conjunction with neuroleptics and/or benzodiazepines to provide more immediate relief of a manic episode. Lithium has also been shown to be effective in regulating bipolar depression, but is not recommended for mixed mania. Lithium may not be an effective long-term treatment option for rapid cyclers, who typically develop a tolerance for it, or may not respond to it. Possible side effects of the drug include weight gain, thirst, nausea, and hand tremors. Prolonged lithium use may also cause hyperthyroidism (a disease of the thryoid that is marked by heart palpitations, nervousness, the presence of goiter, sweating, and a wide array of other symptoms.)
- Carbamazepine (Tegretol, Atretol) is an anticonvulsant drug usually prescribed in conjunction with other mood stabilizing agents. The drug is often used to treat bipolar patients who have not responded well to lithium therapy. Blurred vision and abnormal eye movement are two possible side effects of carbamazepine therapy. As of early 1998, carbamazepine did not have an FDA-cleared indication for mania.
- Valproate (divalproex sodium, or Depakote; valproic acid, or Depakene) is one of the few drugs available that has been proven effective in treating rapid cycling bipolar and mixed states patients. Valproate is prescribed alone or in combination with carbamazepine and/or lithium. Stomach cramps, indigestion, diarrhea, hair loss, appetite loss, nausea, and unusual weight loss or gain are some of the common side effects of valproate. Note: valproate is also approved for the treatment of mania.
Because antidepressants may stimulate manic episodes in some bipolar patients, their use is typically short-term. Selective serotonin reuptake inhibitors(SSRIs) or, less often, monoamineoxidaseinhibitors (MAOinhibitors) are prescribed for episodes of bipolar depression. Tricyclic antidepressants used to treat unipolar depression may trigger rapid cycling in bipolar patients and are, therefore, not a preferred treatment option for bipolar depression.
- SSRIs, such as fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil), regulate depression by regulating levels of serotonin, a neurotransmitter. Anxiety, diarrhea, drowsiness, headache, sweating, nausea, sexual problems, and insomnia are all possible side effects of SSRIs.
- MAOIs such as tranylcypromine (Parnate) and phenelzine (Nardil) block the action of monoamine oxidase (MAO), an enzyme in the central nervous system. Patients taking MAOIs must cut foods high in tyramine (found in aged cheeses and meats) out of their diet to avoid hypotensive side effects.
- Bupropion (Wellbutrin) is a heterocyclic antidepressant. The exact neurochemical mechanism of the drug is not known, but it has been effective in regulating bipolar depression in some patients. Side effects of bupropion include agitation, anxiety, confusion, tremor, dry mouth, fast or irregular heartbeat, headache, and insomnia.
- ECT, or electroconvulsive therapy, has a high success rate for treating both unipolar and bipolar depression, and mania. However, because of the convenience of drug treatment and the stigma sometimes attached to ECT therapy, ECT is usually employed after all pharmaceutical treatment options have been explored. ECT is given under anesthesia and patients are given a muscle relaxant medication to prevent convulsions. The treatment consists of a series of electrical pulses that move into the brain through electrodes on the patient's head. Although the exact mechanisms behind the success of ECT therapy are not known, it is believed that this electrical current alters the electrochemical processes of the brain, consequently relieving depression. Headaches, muscle soreness, nausea, and confusion are possible side effects immediately following an ECT procedure. Temporary memory loss has also been reported in ECT patients. In bipolar patients, ECT is often used in conjunction with drug therapy.
Adjunct treatments are used in conjunction with a long-term pharmaceutical treatment plan:
- Long-acting benzodiazepines such as clonazepam (Klonapin) and alprazolam (Xanax) are used for rapid treatment of manic symptoms to calm and sedate patients until mania or hypomania have waned and mood stabilizing agents can take effect. Sedation is a common effect, and clumsiness, lightheadedness, and slurred speech are other possible side effects of benzodiazepines.
- Neuroleptics such as chlorpromazine (Thorazine) and haloperidol (Haldol) are also used to control mania while a mood stabilizer such as lithium or valproate takes effect. Because neuroleptic side effects can be severe (difficulty in speaking or swallowing, paralysis of the eyes, loss of balance control, muscle spasms, severe restlessness, stiffness of arms and legs, tremors in fingers and hands, twisting movements of body, and weakness of arms and legs), benzodiazepines are generally preferred over neuroleptics.
- Psychotherapy and counseling. Because bipolar disorder is thought to be biological in nature, therapy is recommended as a companion to, but not a substitute for, pharmaceutical treatment of the disease. Psychotherapy, such as cognitive-behavioral therapy, can be a useful tool in helping patients and their families adjust to the disorder, in encouraging compliance to a medication regimen, and in reducing the risk of suicide. Also, educative counseling is recommended for the patient and family.
Calcium channel blockers (nimodipine, or Nimotop), typically used to treat angina and hypotension, have been found effective, in a few small studies, for treating rapid cyclers. Calcium channel blockers stop the excess calcium build up in cells that is thought to be a cause of bipolar disorder. They are usually used in conjunction with other drug therapies such as carbamazepine or lithium.
Clozapine (Clozaril) is an atypical antipsychotic medication used to control manic episodes in patients who have not responded to typical mood stabilizing agents. The drug has also been a useful prophylactic, or preventative treatment, in some bipolar patients. Common side effects of clozapine include tachycardia (rapid heart rate), hypotension, constipation, and weight gain. Agranulocytosis, a potentially serious but reversible condition in which the white blood cells that typically fight infection in the body are destroyed, is a possible side effect of clozapine. Patients treated with the drug should undergo weekly blood tests to monitor white blood cell counts.
Risperidone (Risperdal) is an atypical antipsychotic medication that has been successful in controlling mania in several clinical trials when low doses were administered. The side effects of risperidone are mild compared to many other antipsychotics (constipation, coughing, diarrhea, dry mouth, headache, heartburn, increased length of sleep and dream activity, nausea, runny nose, sore throat, fatigue, and weight gain).
Lamotrigine (Lamictal, or LTG), an anticonvulsant medication, was found to alleviate manic symptoms in a 1997 trial of 75 bipolar patients. The drug was used in conjunction with divalproex (divalproate) and/or lithium. Possible side effects of lamotrigine include skin rash, dizziness, drowsiness, headache, nausea and vomiting.
rTMS, or repeated transcranial magnetic stimulation is a new and still experimental treatment for the depressive phase of bipolar disorder. In rTMS, a large magnet is placed on the patient's head and magnetic fields of different frequency are generated to stimulate the left front cortex of the brain. Unlike ECT, rTMS requires no anesthesia and does not induce seizures.
General recommendations include maintaining a calm environment, avoiding over stimulation, getting plenty of rest, regular exercise, and proper diet. Chinese herbs may soften mood swings. Biofeedback is effective in helping some patients control symptoms such as irritability, poor self control, racing thoughts, and sleep problems. A diet low in vanadium (a mineral found in meats and other foods) and high in vitamin C may be helpful in reducing depression.
While most patients will show some positive response to treatment, response varies widely, from full recovery to a complete lack of response to all drug and/or ECT therapy. Drug therapies frequently need adjustment to achieve the maximum benefit for the patient. Bipolar disorder is a chronic recurrent illness in over 90% of those afflicted, and one that requires lifelong observation and treatment after diagnosis. Patients with untreated or inadequately treated bipolar disorder have a suicide rate of 15-25% and a nine-year decrease in life expectancy. With proper treatment, the life expectancy of the bipolar patient will increase by nearly seven years and work productivity increases by ten years.
The ongoing medical management of bipolar disorder is critical to preventing relapse, or recurrence, of manic episodes. Even in carefully controlled treatment programs, bipolar patients may experience recurring episodes of the disorder. Patient education in the form of psychotherapy or self-help groups is crucial for training bipolar patients to recognize signs of mania and depression and to take an active part in their treatment program.
- Affective disorder
- An emotional disorder involving abnormal highs and/or lows in mood. Now termed mood disorder.
- Anticonvulsant medication
- A drug used to prevent convulsions or seizures; often prescribed in the treatment of epilepsy. Several anticonvulsant medications have been found effective in the treatment of bipolar disorder.
- Antipsychotic medication
- A drug used to treat psychotic symptoms, such as delusions or hallucinations, in which patients are unable to distinguish fantasy from reality.
- A group of tranquilizers having sedative, hypnotic, antianxiety, amnestic, anticonvulsant, and muscle relaxant effects.
- Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). This reference book, published by the American Psychiatric Association, is the diagnostic standard for most mental health professionals in the United States.
- Electroconvulsive therapy is sometimes used to treat depression or mania when pharmaceutical treatment fails.
- A milder form of mania which is characteristic of bipolar II disorder.
- Mixed mania/mixed state
- A mental state in which symptoms of both depression and mania occur simultaneously.
- An elevated or euphoric mood or irritable state that is characteristic of bipolar I disorder.
- A chemical in the brain that transmits messages between neurons, or nerve cells. Changes in the levels of certain neurotransmitters, such as serotonin, norepinephrine, and dopamine, are thought to be related to bipolar disorder.
- Psychomotor retardation
- Slowed mental and physical processes characteristic of a bipolar depressive episode.
For Your Information
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Press, Inc., 1994.
- Maxmen, Jerrold S., and Nicholas G. Ward. "Mood Disorders." In Essential Psychopathology and Its Treatment, 2nd ed. New York: W.W. Norton, 1995, pp. 206-43.
- Whybrow, Peter C. A Mood Apart. New York: Harper Collins, 1997.
- Biederman, Joseph A. "Is There a Childhood form of Bipolar Disorder?" Harvard Mental Health Letter, 13, no. 9 (March 1997): 8.
- Bowden, Charles L. "Choosing the Appropriate Therapy for Bipolar Disorder." Medscape Mental Health, 2, no. 8 (1997). http://www.medscape.com.
- Bowden, Charles L. "Update on Bipolar Disorder: Epidemiology, Etiology, Diagnosis, and Prognosis." Medscape Mental Health, 2, no. 6 (1997). http://www.medscape.com.
- Francis, A., J.P. Docherty, and D.A. Kahn. "The Expert Consensus Guideline Series: Treatment of Bipolar Disorder." Journal of Clinical Psychiatry, 57, supplement 12A (November 1996): 1-89.
- Hirschfeld, Robert "Recent Developments in Clinical Aspects of Bipolar Disorder." The Decade of the Brain: A Publication of the National Alliance for the Mentally Ill, 6, no. 2 (Winter 1995).
- American Psychiatric Association (APA). Office of Public Affairs. 1400 K Street NW, Washington, DC 20005. (202) 682-6119. http://www.psych.org/.
- National Alliance for the Mentally Ill (NAMI). 200 North Glebe Road, Suite 1015, Arlington, VA 22203-3754. (800) 950-6264. http://www.nami.org.
- National Depressive and Manic-Depressive Association (NDMDA). 730 N. Franklin St., Suite 501, Chicago, IL 60610. (800) 826-3632. http://www.ndmda.org.
- National Institute of Mental Health (NIMH). 5600 Fishers Lane, Rm. 7C-02, Bethesda, MD 20857. (301) 443-4513. http://www.nimh.nih.gov/.
Gale Encyclopedia of Medicine. Gale Research, 1999.
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