Until the latter part of the twentieth century, people with bipolar disorders were destined to spend their lives on an emotional roller coaster. Psychotherapists reported almost no success, and antidepressant drugs were of limited help. In fact, the drugs sometimes triggered a manic episode (Courtet, Samalin, & Olié, 2011; Post, 2011, 2005). And ECT only occasionally relieved either the depressive or the manic episodes of bipolar disorders.

This gloomy picture changed dramatically in 1970 when the FDA approved the use of lithium, a silvery-white element found in various simple mineral salts throughout the natural world, as a treatment for bipolar disorder. Other mood stabilizing, or antibipolar, drugs have since been developed, and several of them are now used more widely than lithium, either because they produce fewer undesired effects or because they are even more effective than lithium.

Nevertheless, it was lithium that first brought hope to those suffering from bipolar disorder. Recall the praise for lithium offered by psychiatric researcher Kay Redfield Jamison at the beginning of this chapter. Here Jamison describes in more detail her relationship with the drug and the role it has played in her recovery from bipolar disorder:

The discovery that lithium effectively reduces bipolar symptoms was, like so many other medical discoveries, quite accidental. In 1949 an Australian psychiatrist, John Cade, hypothesized that manic behavior is caused by a toxic level of uric acid in the body. He set out to test this theory by injecting guinea pigs with uric acid, but first he combined it with lithium to increase its solubility.

To Cade’s surprise, the guinea pigs became not manic but quite lethargic after their injections. Cade suspected that the lithium had produced this effect. When he later administered lithium to 10 human beings who had mania, he discovered that it calmed and normalized their mood. Many countries began using lithium for bipolar disorders soon after, but as noted earlier, it was not until 1970 that the FDA approved it.

Determining the correct lithium dosage for a given patient is a delicate process requiring regular analyses of blood and urine samples and other laboratory tests. Too low a dose will have little or no effect on the bipolar mood swings, but too high a dose can result in lithium intoxication (literally, poisoning), which can cause nausea, vomiting, sluggishness, tremors, dizziness, slurred speech, seizures, kidney dysfunction, and even death. With the correct dose, however, lithium often produces a noticeable change (Geddes & Miklowitz, 2013; Grof, 2010). Some patients respond better to the other mood stabilizing drugs, such as the antiseizure drugs carbamazepine (Tegretol) or valproate (Depakote), or to a combination of such drugs (Selle et al., 2014; Altamura et al., 2011). And still others respond best to a combination of mood stabilizers and atypical antipsychotic drugs, medications that you will read about in Chapter 15 (Selle et al., 2014; Nivoli et al., 2011).

Given the effectiveness of lithium and other mood stabilizers, around one-third of all persons with a bipolar disorder now seek treatment from a mental health professional in any given year. Another 15 percent are treated or monitored by family physicians (NIMH, 2014; Wang et al., 2005).

Effectiveness of Lithium and Other Mood StabilizersAll manner of research has attested to the effectiveness of lithium and other mood stabilizers in treating manic episodes (Geddes & Miklowitz, 2013; Grof, 2010, 2005). More than 60 percent of patients with mania improve on these medications. In addition, most such patients have fewer new episodes as long as they continue taking the medications (Malhi et al., 2013; Gao et al., 2010). One study found that the risk of relapse is 28 times higher if patients stop taking a mood stabilizer (Suppes et al., 1991). These findings suggest that the mood stabilizers are also prophylactic drugs, ones that actually help prevent symptoms from developing. Thus, today’s clinicians usually continue patients on some level of a mood stabilizing drug even after their manic episodes subside (Gao et al., 2010).

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In the limited body of research that has been done on this subject, the mood stabilizers also seem to help those with bipolar disorder overcome their depressive episodes, though to a lesser degree than they help with their manic episodes (Malhi et al., 2013; Post, 2011). In addition, continued doses of mood stabilizers may help reduce the risk of future depressive episodes and future suicide attempts, just as they seem to prevent the return of manic episodes (Gao et al., 2010; Carney & Goodwin, 2005). Given the drugs’ less powerful impact on depressive episodes, many clinicians use a combination of mood stabilizers and antidepressant drugs to treat bipolar depression, although research suggests that antidepressants may trigger manic episodes in some cases (Nivoli et al., 2011; Post, 2011; Vazquez et al., 2011).

Mode of Operation of Mood StabilizersResearchers do not fully understand how mood stabilizing drugs operate (Malhi et al., 2013; Aiken, 2010). They suspect that the drugs change synaptic activity in neurons, but in a way different from that of antidepressant drugs. The firing of a neuron actually consists of several phases that ensue at lightning speed. When the neurotransmitter binds to a receptor on the receiving neuron, a series of changes occur within the receiving neuron to set the stage for firing. The substances in the neuron that carry out those changes are often called second messengers because they relay the original message from the receptor site to the firing mechanism of the neuron. (The neurotransmitter itself is considered the first messenger.) Whereas antidepressant drugs affect a neuron’s initial reception of neurotransmitters, mood stabilizers appear to affect a neuron’s second messengers (Gawryluk & Young, 2011).

Different second-messenger systems are at work in different neurons. In one of the most important systems, chemicals called phosphoinositides are produced once neurotransmitters are received. Research suggests that lithium, and perhaps the other mood stabilizers as well, affect this particular messenger system (Malhi et al., 2013; Gawryluk & Young, 2011). It may be that these drugs affect the activity of any neuron that uses this second-messenger system and in so doing correct the biological abnormalities that lead to bipolar disorders.

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In a similar vein, it has been found that lithium and other mood stabilizing drugs also increase the production of neuroprotective proteins—key proteins within certain neurons whose job is to prevent cell death. The drugs may increase the health and functioning of those cells and thus reduce bipolar symptoms (Malhi et al., 2013; Gray et al., 2003).

Alternatively, it may be that the mood stabilizers correct bipolar functioning by directly changing sodium and potassium ion activity in neurons (Swonger & Constantine, 1983). In Chapter 7 you read that bipolar disorders may be triggered by unstable alignments of ions along the membranes of certain neurons in the brain. If this instability is the key to bipolar problems, mood stabilizers would be expected to have some kind of effect on the ion activity. Several studies in fact suggest that lithium ions often substitute, although imperfectly, for sodium ions, and other research suggests that lithium changes the transport mechanisms that move ions back and forth across the neural membrane (Lambert & Kinsley, 2010; Soares et al., 1999; Baer et al., 1971).

Psychotherapy alone is rarely helpful for persons with bipolar disorders. At the same time, clinicians have learned that mood stabilizing drugs alone are not always sufficient either. Thirty percent or more of patients with these disorders may not respond to lithium or a related drug, may not receive the proper dose, or may relapse while taking it. In addition, a number of patients stop taking mood stabilizers on their own because they are bothered by the drugs’ unwanted effects, feel too well to recognize the need for the drugs, miss the euphoria felt during manic episodes, or worry about becoming less productive when they take the drugs (Advokat et al., 2014; Aiken, 2010).

In view of these problems, many clinicians now use individual, group, or family therapy as an adjunct to mood stabilizing drugs (Reinares et al., 2014; Geddes & Miklowitz, 2013; Lee et al., 2011). Most often, therapists use these formats to emphasize the importance of continuing to take medications; to improve social skills and relationships that may be affected by bipolar episodes; to educate patients and families about bipolar disorders; to help patients solve the family, school, and occupational problems caused by their disorder; and to help prevent patients from attempting suicide (Hollon & Ponniah, 2010). Few controlled studies have tested the effectiveness of such adjunctive therapy, but those that have been done, along with numerous clinical reports, suggest that it helps reduce hospitalization, improves social functioning, and increases patients’ ability to obtain and hold a job (Culver & Pratchett, 2010). Psychotherapy plays a more central role in the treatment of cyclothymic disorder, the mild bipolar pattern that you read about in Chapter 7. In fact, patients with cyclothymic disorder typically receive psychotherapy, alone or in combination with mood stabilizers.