Noncompliance with the prescribed medication regimen (e.g., lithium) is a frequent complicating factor in the treatment of bipolar disorder.

QUESTION

Noncompliance with the prescribed medication regimen (e.g., lithium) is a frequent complicating factor in the treatment of bipolar disorder.

1. What are the main reasons that patients with this disorder are inclined to avoid taking their medications, even when they have seen benefits from them?

ANSWER

Bipolar Disorder

At the time of his referral to a psychiatrist working in the outpatient program of a private psychiatric hospital, Buddy King was a 28-year-old married African American man who worked as a manager in a family food business (he had obtained a degree in business administration at the age of 24) and had a wife and two daughters (ages 18 months and 4 years). Buddy was referred by his family doctor after his wife had called the doctor to express concern over her observations that her husband was becoming increasingly depressed. Over the prior 2 to 3 months, Buddy’s symptoms of depression had indeed escalated. These symptoms included sustained depressed mood and lack of energy, difficulties concentrating, decreased interest and withdrawal from the activities he usually enjoyed, pessimistic views and rumination about the future, and sleep disturbance (i.e., awakening in the morning several hours before he intended). More recently, Buddy had experienced a decrease in his interest in sexual relations with his wife, and occasionally he had thoughts about committing suicide.

Despite these escalations in his symptoms of depression, Buddy was hesitant to see a psychiatrist due to his fear of being revealed as “mentally ill” or “weak.” However, these symptoms were beginning to interfere with his work, social life, and marriage. Buddy had previously been very energetic and devoted to his work. He now found it difficult to get up in the morning to go to the office. Furthermore, he had been an avid athlete, but recently he had discontinued nearly all of his athletic activities. Based on these factors, Buddy reluctantly agreed to set up an initial appointment with the psychiatrist.

Clinical History

Buddy’s decision to agree to make this appointment was also influenced by his experiences in college. When Buddy was in his senior year at a prestigious university in the Midwest, he had experienced syniptoms of depression. During this time, Buddy was under a great deal of stress arising from his family (his parents were upset that he was taking too long in college), and his strong concerns about what he would do for a career after graduation. However, unlike Buddy’s more recent experiences (i.e., his symptoms predating his referral to the psychiatrist), these symptoms of depression were followed a few days later by more dramatic symp toms. Specifically, Buddy had experienced a full manic episode, characterized by symptoms of abnormally and persistently elevated mood, grandiose and persecutory delusions, hyperactivity, and a substantially decreased need for sleep (described in more detail later). During this episode, Buddy’s school performance diminished greatly, and he often skipped classes altogether. Although he had previously been a sensible drinker (he only drank socially at college parties), Buddy engaged in several alcohol and marijuana binges.

This manic episode was accompanied by other bizarre and risky activity. During the manic episode, Buddy experienced a marked increase in sexual desire. However, at the time, Buddy was not in a relationship to satisfy his sexual longings. The most significant negative consequence of Buddy’s manic episode was his arrest by campus police after he was found naked with a 15-year-old girl in a vacant office building on campus. Although Buddy was arrested and charged with trespassing, these charges were later dropped. The police also threatened to charge him with sexual misconduct with an underage female, but these charges never materialized.

The morning after his arrest, Buddy was taken to a hospital where he was involuntarily hospitalized with the diagnosis of an acute manic episode. This hospitalization lasted 6 weeks. During the first 2 weeks of hospitalization, Buddy was very resistant to treatment and refused most medications. However, he gradually accepted the notion of medications but refused lithium treatment (lithium carbonate is the most widely used drug for the treatment of mania). He was treated with a combination of Depakote (an antiseizure drug), divalproex (occasionally used in the treatment of mania because it seems to “depress” the central nervous system), and Haldol (haloperidol, an antipsychotic drug used in the treatment of psychotic symptoms such as delusions and hallucinations), which resulted in a gradual reduction in his manic symptoms. At the time of his discharge from the hospital, Buddy insisted on the discontinuation of Haldol, although he reluctantly agreed to continue taking Depakote.

For a time after his discharge, things were rough for Buddy. Although his legal charges were eventually dropped, college authorities refused to allow Buddy to continue in school. Thus, Buddy was forced to transfer and complete his degree at another university. He was somewhat shunned by his friends (who did not understand why Buddy had suddenly acted in a manner so out of character), and his family was very disturbed by the onset of these serious manic symptoms. Although they continually pressured him to comply with his treatment, the family was dismayed that Buddy had become increasingly noncompliant with medical recommendations to continue taking Depakote and submit to regular laboratory tests that were required for his medication regimen (i.e., blood tests that evaluate whether the drug is present at a therapeutic level in the person’s system and that rule out the presence of negative side effects). This resulted in numerous family conflicts and heated discussions between Buddy and his parents. Buddy rejected his parents’ arguments for medication compliance by pointing out that his manic symptoms were no longer present, and so he no longer needed to take the drug.

However, unlike many people who have experienced a manic episode, Buddy, in fact, had had no additional manic episodes since college, even though he had totally stopped taking medications. Buddy completed college at another school and, not having found employment elsewhere, decided to work in the family’s food business (where he continued to work at the time of his referral). During the first year after college, Buddy met the woman he eventually married, and he settled into working in the family business. Although Buddy had not experienced any additional manic episodes, he continued to have brief periods of depression from time to time, none of them long or severe enough to cause Buddy to obtain treatment, although his wife had often urged him to do so. Had it not been for his wife’s urgings, Buddy might have never agreed to the initial appointment with the psychiatrist.

Buddy was born and raised in a very pressured and high-achieving family. His father was a successful food manufacturer who gradually incorporated all of his children in the family business. Buddy was the youngest of five children; he often struggled with competition with his older brothers. He stated that he often felt that he had to “go the extra mile” in order to measure up to his older brothers in his parents’ eyes. Buddy’s father was a somewhat harsh, yet supportive man who demanded performance and conscientiousness from all of his children. Differences of opinion were not well-tolerated in the family, and each child was pressured to agree with parental views. Although the family was very wealthy, much of the parents’ support (both emotional and financial) was tied to such compliant attitudes. For example, those children who rebelled (e.g., had differing views on how aspects of the family business should be run) were often ostracized and would later rejoin after agreeing to give up their “rebellious” attitudes. Buddy described himself as being hyper-conscientious and driven during his childhood years, a characteristic that he attributed to his family environment. He also recalled being perfectionistic in high school and college athletics (he played on the basketball team) and to some degree in his school work. Buddy claimed that these family dynamics had resulted in several recent conflicts regarding decisions within the family food business, which he cited as possible contributing factors to his current depression.

Buddy’s family had various members with mood disorders. His mother had recurring bouts of depression that had been treated with antidepressant medications. Buddy’s maternal grandmother, paternal uncle, and oldest brother had also received outpatient treatment for depression. Buddy’s maternal uncle had alcoholism and possible bipolar disorder, although the presence of this latter diagnosis was uncertain because he was estranged from the family and lived in another part of the country.

DSM-5 Diagnosis

Based on the information presented, Buddy was assigned the following DSM-S (Diagnostic and Statistical Manual of Mental Disorders, 5th ed.) diagnosis: 296.52 Bipolar I disorder, current or most recent episode depressed, moderate Bipolar disorder is the formal diagnostic term for a condition that has been more commonly referred to by laypersons as “manic depression.” Although Buddy did not show any signs of mania at the time of his referral to the psychiatrist, the diagnosis of bipolar disorder is still appropriate because he had a history of a full manic episode. In DSM-S (AmericÄn Psychiatric Association, 2013), a manic episode is defined as a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy that is accompanied by at least three of the following symptoms:

(a) inflated self-esteem or grandiosity,

(b) decreased need for sleep (e.g., feeling rested after only 3 hours of sleep),

(c) more talkative than usual or pressure to keep talking,

(d) flight of ideas (e.g., jumping from one topic to another in midconversation) or subjective experience that thoughts are racing,

(e) distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli),

(f) increase in goal-directed activity (e.g., writing a torrent of letters to public figures or friends, taking on new business ventures) or psychomotor agitation (e.g., constant pacing, carrying on several conversations at the same time), and

(g) excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., buying sprees, foolish business investments, or, as in Buddy’s case, sexual indiscretions). To qualify as a manic episode, the disturbance must last at least 1 week or can be of any duration if hospitalization is necessary (as was the case with Buddy).

When establishing a diagnosis, the clinician must make the distinction between manic and hypomanic episodes. In DSM-5, both manic and hypomanic episodes have the same characteristic symptoms listed in the preceding paragraph. However, the two types of episodes are distinguished primarily by the extent to which they are accompanied by lifestyle impairment. In contrast to a manic episode, a hypomanic episode is not severe enough to cause marked impairment in social or occupational (or academic) functioning and does not require hospitalization. Moreover, the duration criterion for a hypomanic episode is briefer (4 days or more) than for a manic episode (at least 1 week). The presence of at least one lifetime manic episode is required for the DSM-S diagnosis of bipolar I disorder. Hypomanic episodes are common in bipolar I disorder but are not required for this diagnosis.

If a person presents to a clinic with current or past manic symptoms, a number of potential DSM-5 diagnoses may be applicable. As noted above, if the person has experienced symptoms that meet criteria for a full manic episode, the diagnosis of bipolar I disorder is appropriate (as was the case for Buddy). Although the term bipolar may imply otherwise (i.e., two poles of mood from extremely high to extremely down), the diagnosis of bipolar I disorder is still appropriate if the person has experienced a manic episode but not a major depressive episode. However, presentations involving full manic episodes only are infrequent, and most patients with bipolar I disorder experience alterations in mood cycling between manic episodes and major depressive episodes (often separated by periods of normal mood).
The diagnosis of bipolar Il disorder is used in reference to clinical presentations of one or more major depressive episodes and at least one hypomanic episode (and no history of full manic episodes). The defining feature of the diagnosis cyclothymic disorder is the chronic (at least 2 years) presence of numerous periods of hypomanic symptoms and numerous periods of depressive symptoms that are not severe  enough to meet criteria for a hypomanic episode and a major depressive episode, respectively. If the person has at any time met criteria for major depressive, manic, or hypomanic episodes, the diagnosis of cyclothymic disorder is not assigned.

As you may have noted from Buddy’s diagnosis, his bipolar disorder was assigned with two specifiers (i.e., “current or most recent episode depressed,” “moderate”). In addition to the use of specifiers to convey the severity of the disorder (e.g., “mild,” “moderate, severe, with psychotic features”), there are specifiers included with the diagnosis of bipolar disorder to describe the nature and course of the disturbance. Specifically, because most persons with this disorder cycle between periods of depression and mania, a specifier is used to indicate the person’s current or most recent mood state (e.g., “current or most recent episode manic”). When applicable, additional specifiers can be assigned to better convey the nature of the disturbance. An example of one such specifier is “with rapid cycling,” which is used to characterize presentations where 4 mood episodes (meeting the criteria for manic, hypomanic, or major depressive episode) have been experienced in the previous 12 months. The mood episodes can occur in any combination and in any order.

CASE FORMULATION USING THE INTEGRATIVE MODEL

Like each of the anxiety and mood disorders discussed in this book, the integrative theory of bipolar disorders is based on a diathesis-stress model (Barlow & Durand, 2015). The “diathesis” component of the integrative model refers to the biological vulnerability to develop a bipolar disorder. Although no specific genetic or biological markers have been confirmed as risk factors for bipolar disorders, at present this vulnerability seems to be best described as an overactive neurological response to stressful life events (the “stress” component of the diathesis-stress model). Although some research suggests that the bipolar, mood, and anxiety disorders share a common, genetically determined biological vulnerability (e.g., Kendler, Neale, Kessler, Heath, & Eaves, 1992b), there is some evidence that the genetic basis for bipolar disorder is distinct from the inheritability of mood disorders (Nurnberger, 2012).

Evidence of the presence of this genetic vulnerability in Buddy was his extensive family history of depression (and possibly bipolar disorder). This is consistent with research findings showing that the rate of mood disorders in the families of persons with bipolar disorder is considerably higher than the rate among other families (Lau & Eley, 2010). However, one interesting result emerging from these studies is that the most frequent mood disorder in the relatives of persons with bipolar disorder is not bipolar disorder but rather major depression. For persons with major depression, there seems to be a negligible chance that their relatives will have a greater incidence of bipolar disorder than will people with no emotional disorder. Thus, among the mood disorders, there may not be a specific or separate genetic contribution to bipolar disorder. Instead, bipolar disorder may represent a more severe manifestation of this underlying genetic vulnerability. This manifestation would be determined by other psychosocial or biological factors that occur in addition to genetic vulnerability. This connection is not y_et certain, and researchers have long disagreed as to whether bipolar disorder and major depression are two distinct disorders or one disorder that varies in its severity (Angst & Sellaro, 2000; Blehar, Weissman, Gershon, & Hirschfeld, 1988; Nurnberger, 2012).

Findings from twin studies have also supported the role of genetics in the origins of bipolar disorder. For example, in a study by Bertelsen, Harvald, and Hauge (1977), if one twin had bipolar disorder, there was an 80% chance that a monozygotic (identical) twin had some form of mood or bipolar disorder (e.g., major depression, bipolar disorder). This was substantially higher than the rate of mood disorders (16%) in dizygotic (fraternal) twins, if one twin had bipolar disorder. As monozygotic twins have exactly the same genes and dizygotic twins share only about 50% of each other’s genes (the same amount shared among first-order relatives), the higher rate of mood disorders in monozygotic twin pairs suggests that genetic factors contribute to the development of bipolar disorder. However, subsequent studies have observed somewhat weaker concordance rates in twin pairs compared to those obtained by Bertelsen et al. (1977) (e.g., McGuffin & Katz, 1989; McGuffin et al., 2003), although in general the genetic contributions for bipolar disorder appears to be stronger than for depressive disorders.

Numerous studies have attempted to identify neurobiological factors contributing to the development and maintenance of bipolar disorder. Despite this issue’s considerable research attention, no neurobiological component has been linked with certainty to this disorder. Researchers generally concur that the balance among a variety of neurotransmitters is more important than the absolute level of any one neurotransmitter in bipolar disorder. For instance, there is increasing interest in the role of dopamine in the context of this balance among neurotransmitters, based on evidence that drugs that increase the activity of dopamine (dopamine agonists” such as L-dopa) produce mild manic-like states (i.e., hypomania) in patients with bipolar disorder (Anand et al., 2000; Dunlop & Nemeroff, 2007).

Additionally, research has shown that patients with bipolar disorder and their children (who are at greater risk for bipolar disorder) show increased sensitivity to light, that is, when exposed to light at night, they show greater suppression of the hormone melatonin (Nurnberger et al., 1988). Melatonin is a hormone activated by darkness to control the body’s biological clock and to induce sleep. There is also evidence that extended bouts of insomnia trigger manic episodes (MalkoffSchwartz et al., 2000; Wehr, Goodwin, Wirz-Justice, Breitmeier, & Craig, 1982). These findings suggest that onsets of bipolar disorder are related to disruptions in circadian rhythms (resulting from low levels of the neurotransmitter serotonin; cf. Goodwin & Jamison, 2007).

Other evidence of the role of neurotransmitters in bipolar disorder comes from a host of studies and clinical observations attesting to the effectiveness of the drug lithium in the treatment of this condition. A detailed description of lithium is provided in the next section. The fact that many patients with bipolar disorder respond favorably to lithium has been viewed by some researchers as indicating that the drug is regulating the levels of neurotransmitters contributing to bipolar disorder. However, it is not clear how lithium works. It is possible that lithium reduces the availability of the neurotransmitters dopamine and norepinephrine. Yet, it has also been hypothesized that lithium affects the endocrine system, particularly neurochemicals that affect the production and levels of sodium and potassium, which are electrolytes found in our body fluids (Goodwin & Jamison, 2007). Much more research is needed to identify lithium’s mechanisms of action. These findings could potentially lead to more effective drug treatments for bipolar disorder, in addition to a greater understanding of the neurobiological factors contributing to this disturbance.

As noted in the beginning of this section, stressful life events appear to play a significant role in the onset of mood disorders and manic episodes. A large body of research indicates that stressful life events (family difficulties, job loss, etc.) are strongly related to the onset of mood disorders, particularly major depression. A few studies have also produced data that support the connection between stress and the onset of manic episodes (Goodwin & Jamison, 2007; Hammen & Gitlin, 1997). These findings are consistent with Buddy’s experiences, as he connected the emergence of his first manic episode (and subsequent periods of depression) to stress in his life (e.g., senior year of college, familial conflict on how the family business should be run). The limited data that do exist on the role of stress in bipolar disorder suggest that while stressful life events may trigger initial manic episodes, once the disorder develops, these episodes take on a life of their own and occur with no obvious connection to life stress (Post, 1992). According to current diathesis-stress models, stress contributes to the development of bipolar disorder because stressful life events activate our stress hormones, which, in turn, have wide-ranging effects on our neurotransmitter systems (e.g., serotonin, norepinephrine, dopamine). If these stress hormones remain activated, structural and chemical changes in the brain may occur (e.g., atrophy of neurons in the areas of the brain that contribute to the regulation of emotions and neurotransmitter activity). For instance, the extended effects of stress may be associated with disruptions in a per son’s circadian rhythms, causing them to be susceptible to the recurrent cycling that is a defining feature of many mood disorders. As noted earlier, another psychosocial precipitant of mania appears to be loss of sleep (as might occur in the postpartum period following childbirth), supporting the notion that the emergence of bipolar disorder may be related to a disruption of circadian rhythms (Goodwin & Jamison, 2007).

Many of the psychosocial features that contribute to the onset and maintenance of major depression (e.g., social support; negative perceptions of one’s self, world, and future; sense of helplessness or hopelessness) may also play a significant role in bipolar disorder. Because many of these features are discussed in detail in Case 9, the remainder of this section will focus on factors that are more specific to bipolar disorder. One important factor that may contribute to the maintenance of bipolar disorder and predict a poor treatment response is denial or minimization of the problem. Unlike most of the other disorders discussed in this book, the manic or hypomanic aspect of bipolar disorder is often associated with low subjective distress. Patients may find the “high” of a episode to be so pleasurable that they consider their symptoms and behavior perfectly reasonable and fail to see the need for treatment. Moreover, this factor is often associated with poor compliance with drug treatment. Specifically, some individuals stop taking their prescribed medications during periods of distress and depression in an attempt to bring on the manic state once again.

This feature was clearly evident in Buddy. During the initial portion of his hospital admission, Buddy did not comply with treatment (he refused all medications).

Although he eventually conceded to medications, he quickly stopped taking them following his discharge (against medical advice) because he downplayed the likelihood of his need to continue them to prevent future manic and depressive episodes.

Treatment Goals and Planning

The key intervention that the psychiatrist planned to use in the treatment of Buddy’s mood disorder was medication. Because Buddy’s principal complaint was depression and because he had experienced only a single manic episode several years ago, the psychiatrist opted to initiate treatment with the tricyclic antidepressants (a group of medications that block the reuptake of neurotransmitters such as serotonin and norepinephrine). Another reason for this strategy was Buddy’s refusal to consider taking lithium carbonate, a medication that is commonly used in the treatment of patients with bipolar disorder. Lithium is a common salt that is widely available in the natural environment. For example, it is found in our drinking water in amounts that are too small to have any effect. As noted earlier, in therapeutic doses, lithium is often effective in treating and preventing manic episodes. However, the side effects of therapeutic doses of lithium are potentially more serious than those of other antidepressants. The dosage of lithium has to be carefully regulated to prevent toxicity (poisoning) or thyroid problems (lowered thyroid function in particular) that can increase patients’ lack of energy associated with their depression. Substantial weight gain is another common side effect of this drug. In addition to the potential for side effects, Buddy’s resistance to lithium was based on his difficulty in accepting the diagnosis of bipolar disorder. Although Buddy was resistant to any form of medication treatment, he was especially reluctant to taking lithium because he believed that people who needed lithium must have severe mental illness (based on his limited knowledge from hearing or reading about the uses of lithium on television shows or news articles). This issue is discussed in more detail in the next section.

In addition to pharmacotherapy with antidepressant drugs, Buddy’s treatment plan included supportive and cognitive-behavioral therapy. The psychosocial aspect of treatment would address such issues as Buddy’s acceptance of the problem and of his need to comply with treatment, his withdrawal from social and occupational activities, identification of sources of family stress, and learning ways to cope effectively with these stressors.

Course of Treatment and Treatment Outcome

This section presents a brief summary of Buddy’s treatment, which occurred over the span of 8 years. Because of Buddy’s refusal to take lithium, the psychiatrist proceeded cautiously with the initiation of tricyclic antidepressant medication. The reason for his caution was that these medications, while potentially effective in reducing Buddy’s depression, might possibly induce another manic episode in Buddy if too much of the drug was prescribed. In fact, research has shown that tricyclic antidepressants may induce manic episodes in persons with depression who do not have a preexisting bipolar disorder (Goodwin & Jamison, 2007; Prien et al., 1984). Thus, Buddy had to be closely monitored while he was on the drug, and he had to comply fully with the prescribed medication regimen.

Buddy, in fact, complied very well with the moderate dose of antidepressant medication he was prescribed. Within a few weeks, his symptoms of depression decreased substantially. After his favorable response, he was maintained on a slightly lower dosage of the drug for several months. After 7 months had passed without a recurrence of his depression (and without any signs of mania), Buddy was slowly weaned off the medication. During the first few months, when Buddy was taking a maintenance dosage of antidepressant medication, he also saw the psychiatrist regularly for supportive psychotherapy (the same psychiatrist who monitored Buddy’s response to the drug). These sessions occurred with decreasing frequency over the last couple of months that Buddy was taking the medication. After he had fully discontinued the medication without signs of the depression returning, Buddy and his psychiatrist mutually agreed to terminate their sessions of supportive psychotherapy.

Over the next 18 months, Buddy experienced very few symptoms of depression. Although occasional conflicts within the family continued over how certain aspects of the family business should be managed, Buddy found that his sense of devotion and enthusiasm for his work had returned. In fact, he was given a promotion to be the head of a division within the family business. Although Buddy initially was very gratified by his change in job status, he soon experienced a great deal of stress arising from the marked increase in responsibilities that his promotion entailed. In addition, because Buddy was in a position of greater responsibility that required him to make more decisions about the business, he found himself in increasing conflict with one of his older brothers, who often questioned his decisions (partly because his brother had not adjusted well to the fact that Buddy was now at a level of management that was equal to his).

As these stressors continued, Buddy began to notice that he had difficulty fall ing and staying asleep. Shortly thereafter, he became extremely hyperactive and started having grandiose and suspicious thoughts (grandiose and persecutory delusions), coinciding with changes in his mood that varied between feeling expansive and “on a high” to feeling irritable. He began to work at a feverish pace, often staying at the office 15 to 18 hours a day. He started to develop plans to expand his division of the business to various parts of the country. Increasingly, Buddy was convinced that only he could lead the family business in the direction where it needed to go. Buddy felt that he was “at the top of his game” (grandiose delusions).

However, these plans were considered unrealistic and impractical by his family and coworkers. Buddy became irritated and uncharacteristically enraged with his coworkers and subordinates, who he believed were plotting against him and talking about him behind his back (persecutory delusions). Buddy experienced a gradual increase in the speed of his thoughts. Others noticed that he had become quite distractible and that his speech had become very loud and rapid (pressured speech). Often, in the middle of a conversation about the business, Buddy would utter things that were either nonsensical or totally off the topic (e.g., off-color jokes). When his coworkers tried to give Buddy corrective feedback on his inappropriate behavior, he became very irritated with them and felt that any problem was with them, not him. Consequently, the coworkers began to mistrust Buddy’s leadership and approached other members of the family to discuss the importance of controlling some of his actions. Buddy’s family, his wife in particular, continually urged Buddy to contact his psychiatrist. Buddy refused and denied the significance of his symptoms. Learning that some of his coworkers had consulted with his family about his conduct in the office had the effect of fanning the flames of his suspicion that people were plotting against him. Buddy’s delusions intensified to the point where the family found his behaviors impossible to tolerate. Because Buddy had vehemently refused to seek treatment (even in the face of his wife’s threat of marital separation), his wife finally telephoned the psychiatrist behind Buddy’s back. The psychiatrist, alarmed at the news that Buddy had been in a full manic episode for nearly 2 weeks, ordered him to be involuntarily admitted to the hospital.

The first few days of Buddy’s hospitalization were somewhat reminiscent of his hospital stay during college. However, although Buddy was reluctant to take lithium, he finally accepted this intervention. He quickly responded to the drug and was released from the hospital 8 days later. A central aspect of Buddy’s hospital discharge plan was to have him continue on a maintenance dosage of lithium and visit the psychiatrist regularly for individual psychotherapy and drug monitoring. Although Buddy initially complied with this plan, he soon began to attend these sessions quite erratically. The psychiatrist believed that Buddy’s resistance to treatment was due in large part to his feeling ashamed, weak, and stigmatized by his bipolar disorder. For the most part, Buddy had accepted his history of depression (because “it is not too unusual for a person to feel down from time to time”) but found it very hard to acknowledge his past symptoms of mania, which he regarded as very weird and indicative of significant mental illness. During times when he was not experiencing symptoms of depression or mania, Buddy felt that there was no need to continue using lithium (which served as an unwelcome reminder that he had acted so strangely in the past). The psychiatrist worked hard to assist Buddy to accept his diagnosis (e.g., by challenging his beliefs that the presence of the diagnosis was suggestive of a mental defect or indicated that he was fundamentally different from everyone else) and to accept the need for continued use of lithium to prevent the occurrence of future manic episodes. Buddy finally voiced his agreement with his psychiatrist’s statements, although he did so mainly to placate him. A few months after his hospital discharge, Buddy stopped coming to his outpatient sessions and he stopped taking lithium.

Three months later, Buddy experienced a hypomanic episode. Unlike past incidents when he had experienced manic symptoms, Buddy quickly agreed to his family’s pleas to reinitiate treatment. His psychiatrist promptly put him back on lithium, which again produced a rapid therapeutic response. The fact that he had yet another manic-like episode finally convinced Buddy of the need for compliance with treatment. This realization proved to be one of the most important aspects of Buddy’s treatment. From then on, Buddy gradually accepted his problem and learned to manage his medications adequately and responsibly. Buddy worked with his therapist to learn to identify the first signs of mood disorder symptoms so that drug and psychosocial interventions could be deployed promptly to prevent an escalation into a full manic or depressive episode. Following several treatment sessions that his wife attended, Buddy enlisted his wife and the rest of his family to help in this endeavor (i.e., monitor early signs of symptom recurrence)

Over the next 4 years, Buddy attended all scheduled follow-up sessions, which focused on monitoring and adjusting his dosages of lithium. Once his symptoms and medication were stabilized, these sessions were scheduled less frequently. During this period, Buddy occasionally called his psychiatrist when he was worried about the potential recurrence of symptoms or when he had questions about adjusting his medication to protect against the return of symptoms. Clearly, Buddy’s attitude and behavior now differed markedly from his initial presentation, when he resisted treatment, nrdications, and his diagnosis. This change in attitude was also evident when Buddy developed complications from extended lithium treatment. For example, at one point in treatment, Buddy developed some rashes from the lithium therapy. This side effect was managed through a consultation with a dermatologist. At no time did Buddy use this complication to question the wisdom of continuing on lithium.

Buddy became self-sufficient in maintaining adequate pharmacological protection against further relapses of manic and depressive symptoms (he learned to adjust his medications accordingly in response to early signs of symptom recurrence). During the last 3 years that the psychiatrist worked with him, Buddy attended sessions on a biyearly basis for medication maintenance checks, renewal of prescriptions, and laboratory blood tests. Although Buddy had initially been very resistant to lithium treatment, the psychiatrist believed that Buddy ultimately exhibited one of the most profound beneficial responses to this medication that he had seen in patients with bipolar disorder (making Buddy a somewhat atypical case of bipolar disorder in terms of his treatment response; see the discussion section). Over the 6 years since Buddy had been stabilized on lithium (the time this case was written), he has shown no further signs of manic or depressed symptoms. Buddy went on to form his own food company, which he now directs. He has productively developed new business ventures that continue to prosper. Despite these new occupational responsibilities, Buddy has become more involved in leisure activities. Often, he is able to interrupt his once-driven work habits to spend more time with his wife and children.

DISCUSSION

A population-based survey of more than 9,000 people from ages 18 and older estimated that 3.9% had experienced a bipolar disorder (either bipolar I or bipolar Il) at some time during their lives and that 2.6% had experienced a bipolar disorder within the prior year (Kessler, Berglund, et al., 2005; Kessler, Chiu, Demler, & Walters, 2005). Unlike major depression, which is much more prevalent in females, bipolar I disorder is about equally common in men and women (Kessler et al., 1994; Merikangas & Pato, 2009), although bipolar Il disorder appears to be more common in women. There are no known differences among racial groups in the prevalence of either bipolar I or bipolar Il disorder.

Research has found that the median age of onset for bipolar disorder is about 25 years of age, although onset can occur in childhood (Kessler, Berglund, et al.,2005; Merikangas & Pato, 2009). In fact, a considerable number of cases of bipolar disorder begin in adolescence (as many as one-third; Goodwin & Jamison, 2007; Merikangas et al., 2007). However, there is often a 5- to 10-year interval between the age of onset of symptoms and the age at first treatment or first hospitalization. Bipolar disorder may begin more abruptly than major depression (Angst & Sellaro, 2000; Winokur, Coryell. Endicott, & Akiskal, 1993). However, the typical pattern of onset in males and females appears to differ. The first episode in males is more likely to be a manic episode, whereas in females the first episode is more likely to be depression. Frequently, a person experiences several episodes of depression before a manic episode occurs (Goodwin & Jamison, 2007). Up to a quarter of persons with bipolar Il disorder will eventually progress to bipolar I disorder (e.g., Birmaher et al., 2009).

Once the disorder appears, the course is chronic. Untreated persons with bipolar disorder may have more than 10 total episodes of mania and depression during their lifetime, with the duration of episodes and inter-episode symptom-free periods often stabilizing after the fourth or fifth episode (Goodwin & Jamison, 2007). For women with bipolar I disorder, a higher risk for subsequent episodes is present in the immediate postpartum (after childbirth) period. Often 5 or more years may pass between the first and second episode, but the time periods between subsequent episodes usually narrow. However, it should be emphasized that the variable and episodic nature of bipolar disorder is a hallmark and a unique feature of this condition, as was evident in Buddy, whose initial manic episode emerged abruptly in his senior year of college and was not followed by subsequent episodes until several years later.

Bipolar disorder usually produces substantial disruptions in the afflicted person’s life. For instance, marital discord is a common associated feature. Divorce rates are much higher in persons with bipolar disorder, approaching two to three times the rate in persons without emotional disorders. Compared to persons without emotional disorders, the occupational status of persons with bipolar disorder is twice as likely to deteriorate (Coryell et al., 1993). Persons with bipolar disorder often meet criteria for other disorders; for example, the substance use disorders and the anxiety disorders are quite prevalent in these individuals (Goodwin & Jamison, 2007; Kessler, Chiu, et al., 2005).
Suicide is an unfortunately common associated feature of bipolar disorder. Among patients with emotional disorders, patients with bipolar disorder have among the highest risks for suicide (Fawcett et al., 1987; Goodwin & Jamison, 2007). Estimates of suicide in bipolar disorder range from 8% to as high as 60%, with an average rate of about 19% (e.g., Angst & Sellaro, 2000; Goodwin & Jamison, 2007). Suicide occurs more often in males than in females and is most likely to occur during a depressive episode. Persons with bipolar disorder who also have coexisting substance abuse or anxiety disorders are at substantially greater risk of suicide and poor long-term treatment outcome (e.g., Keller, Lavori, Coryell, Endicott, & Mueller, 1993).

The medication lithium is currently the treatment of choice for bipolar disorder. Results indicate that 50% of patients with bipolar disorder respond well to lithium initially (Goodwin & Jamison, 2007). Thus, while lithium is effective, many patients do not show meaningful improvement. However, for the patients who show a favorable acute response, some studies suggest that lithium is usually effective in preventing future manic and depressive episodes. For example, a review of 10 well-done treatment outcome studies indicated that patients taking lithium had a significantly lower probability of having future episodes than patients taking a placebo. Overall, 34% of the patients taking lithium had additional manic or depressive episodes during the follow-up period, compared to 81% of the patients taking placebo (Goodwin & Jamison, 2007). Lithium maintenance treatment has also been found to lower the frequency of suicide attempts and completions (MüllerOerlinghausen, Muser-Causemann, & Volk, 1992). In fact, whereas untreated bipolar disorder may be associated with a mortality rate that is two to three times higher than that of the general population, some studies have found that the mortality rate of patients in long-term lithium treatment does not differ from that of persons without emotional disorders (e.g., Coppen et al., 1991).

However, a handful of studies examining longer follow-up periods (e.g., 5 or more years) have found less encouraging results of the long-term maintenance effects of lithium (e.g., Gitlin, Swendsen, Heller, & Hammen, 1995; Keller et al., 1993). As noted earlier in this case, one problem associated with lithium treatment (or with any drug treatment, for that matter) is noncompliance. Noncompliance with drug treatment is a major cause of relapse in patients with bipolar disorder (Colom, Vieta, Tacchi, Sanchez-Moreno, & Scott, 2005). Patients with bipolar disorder may be noncompliant with drug therapy for a number of reasons, including denial or failure to believe that they have an emotional disorder (a factor relevant in Buddy’s treatment), reluctance to give up the pleasurable experience of mania, and drug side effects. Indeed, as was true for Buddy, up to 75% of patients treated with lithium experience some side effects (Goodwin & Jamison, 2007).

In addition to lithium, several other medications have proven to be of some benefit. For instance, patients who are nonresponsive or intolerant to lithium may benefit from certain antiseizure medications, such as valproate and carbamazepine (Thase & Kupfer, 1996). Recall that Buddy was initially treated with an antiseizure medication, due in part to his refusal to take lithium. Indeed, valproate has overtaken lithium as the most commonly prescribed mood stabilizer (Goodwin et al., 2003; Keck & McElroy, 2002). However, lithium should still be considered the drug of choice for bipolar disorder because evidence indicates that valproate is considerably less effective than lithium in preventing suicide (e.g., Goodwin et al., 2003; Thase & Denko, 2008; Tondo, Jamison, & Baldessarini, 1997). Electroconvulsive therapy (ECT), while typically associated with severe major depression, has also been found to be effective in treating manic episodes (Mukherjee, Sackeim, & Schnuur, 1994). Additionally, many research psychiatrists believe that ECT should be considered as a primary treatment for the depressed phase of bipolar disorder whenever a rapid response is necessary (e.g., due to marked suicidal ideation and intent) or when drug treatments are contraindicated (e.g., in pregnancy, In patients who have not responded to lithium or antiseizure medication; American Psychiatric Association, 1994, 2010).

Psychological treatments for bipolar disorder have not been widely studied. However, the importance of these interventions IS increasingly recognized. Specifically, researchers have recognized the potential benefits of these treatments to foster compliance with medications (Colom et al., 2005), to address the psychosocial consequences and stress triggers of the disorder (e.g., occupational, marital), and to treat coexisting disorders (e.g., substance use, anxiety disorders) that are associated with an unfavorable long-term course and treatment response (Miklowitz, 2014). Although lithium was the primary factor in Buddy’s favorable treatment response, the psychological component of his therapy was very important in addressing acceptance of his problem, dealing with the social (and marital) consequences of his symptoms, and enlisting persons in his social environment (wife, parents, sib lings) to assist him in detecting the early-signs of possible relapse.

Although a few reports have appeared in the literature on the effects of psychological treatments alone in the treatment of bipolar disorder, most research has examined the effectiveness of these treatments combined with drug treatment. For example, a pilot study has examined the impact of the addition of family therapy and psychoeducation to standard drug treatment on the long-term outcome for bipolar disorder (Miller, Keitner, Epstein, Bishop, & Ryan, 1991). Compared to patients who received drug treatment alone, patients who received family therapy and psychoeducation plus drugs had lower rates of family separations, greater improvements in the level of family functioning, and lower rates of rehospitalization over the 2 years following treat ment. Moreover, the patients receiving psychological treatment also had higher rates of full recovery (56%) than patients receiving medications only (20%). These initial findings suggest that the addition of psychological elements to the treatment of bipolar disorder holds promise for improving the short- and long-term effectiveness of our current interventions. Indeed, other adjunctive psychosocial interventions, such as family-based treatments, treatments aimed at fostering lifestyle regularity (e.g., maintaining regular sleep and other daily schedules), and cognitive therapy have also been shown to augment the long-term benefits of pharmacotherapy of bipolar disorder (e.g., Frank et al., 1997, 1999; Lam, Hayward, Watkins, Wright, & Sham, 2005; Miklowitz, George, Richards, Simoneau, & Suddath, 2003; Simoneau, Miklowitz, Richards, Saleem, & George, 1999).