Clinical Practice Guidelines for Bipolar Disorder

MANAGEMENT OF PERSONS WITH PSYCHOSES
Bipolar/Schizoaffective Disorder Core Annotations

MODULE D

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INTRODUCTORY NOTES

1. Age at onset and symptoms of a mood disorder, including bipolar disorder, can occur at any stage of the life cycle, from prepubescence to senescence. Given the aging VA population, it is important to be sensitive to the fact that the onset of bipolar disorder may frequently occur in the latter decades of life. Further, it is a misconception that bipolar disorder may "burn out" and not require treatment in the geriatric age group; on the contrary, diagnosis and management may become more difficult with the development of age-related behavioral disorders such as the dementias. Equally important, the management of established bipolar disorder may be complicated by factors associated with aging, such as the development of medical problems or administration of multiple medications that increase the risk for drug toxicity.

   The conception and development of these Guidelines are based on principles of assessment and management with particular emphasis in geriatrics. Problem-prone areas dealing with psychosis include administration of medications in situations of reduced renal or hepatic clearance, and administration of medications that interact with commonly prescribed medications for conditions prevalent in older age groups. Readers are referred for further information to a recent review by Baldessarini et al. (1996).

2. Formal instruments are highly recommended when feasible for making the diagnosis of bipolar disorder and for assessing symptom severity and outcome. These guidelines do not endorse any one instrument, although several examples of each type of instrument are provided and are summarized in Table 1.

   For diagnosis, the Structured Clinical Interview for DSM-IV (SCID) (First et al. 1996) is the gold standard. It is helpful both in establishing the diagnosis in unclear cases and in rule in or rule out comorbid conditions which can often be overlooked during unstructured interviews. However, the SCID may be relatively insensitive to diagnosing hypomania (Dunner & Tay 1993). Further, administration can take 1 to 2 hours, depending on complexity. A modified and annotated structured instrument based on the DSM-IV diagnoses has been developed for educational and clinical use in the VA. This instrument, the Teaching Interview for Psychiatric Students (TIPS) (Lambert & Petty 1996), is shorter than the SCID and can be used as a guide for routine, brief clinical evaluations.

   Comprehensive assessment of illness severity and outcome in bipolar disorder involves assessment across three domains: disease-specific outcome (symptoms and episodes); functional outcome (social and occupational role function and health-related quality of life); and economic outcome (direct and indirect illness costs) (Bauer & McBride 1996; Bauer et al. 1997). Only the first of these will be reviewed here, and the reader can pursue the latter two domains through the above references.

   Assessment of clinical symptoms of bipolar disorder is complex, requiring assessment of manic, depressive, and psychotic symptoms. Instruments to determine the complexity of the disorder are of two main types: clinician-rated and self-report.

   Clinician-rated scales for manic symptoms include the Clinician-Administered Rating Scale for Mania (CARS-M) (Altman et al. 1994), and the Young Mania Rating Scale (YMRS) (Young et al. 1978) which are well-validated and widely used. Among depression scales that are clinician-rated, the Hamilton Depression Rating Scale (HDRS) (Hamilton 1990) is probably the most widely used. However, it should be supplemented with queries for atypical depressive symptoms (e.g., hypersomnia, hyperphagia) that are common in bipolar depressive episodes. Numerous addenda with varying levels of validation have been peer-elicited. Perhaps the best-validated queries derive from the Structured Interview Guide for the Hamilton (SIGH-SAD) (Williams 1988) which is a widely used instrument in the assessment of clients with seasonal affective disorder (SAD). Among instruments for psychotic symptoms, the Brief Psychiatric Rating Scale (BPRS) (Overall & Gorman 1962) is the most commonly used.

   Self-reports reflect client experience and provide the advantage of taking less clinician time and being able to be administered frequently, which can be useful for identifying and tracking rapid cycling. There are numerous self-report scales for depression, some of which are available in the Mental Health Package on the Decentralized Hospital Computer Program (DHCP), such as the Beck Depression Inventory (BDI) (Beck et al. 1961).

   Two self-report instruments developed specifically for bipolar disorder are the Life Chart method (Post et al. 1988) and the Internal State Scale (ISS) (Bauer et al. 1991). The Life Chart method integrates disease-specific and functional status. With clinician assistance it can also be used to map out the course of disease retrospectively. The ISS has subscales for both manic and depressive symptoms and therefore can be useful in assessing mixed states as well as classic mania and depression. The ISS also contains a subscale highly correlated with the BPRS. Note that simple visual analog (unmarked line) or Likert (1 to 10) scales anchored by "Best" for mania and "Worst" for depression, are not recommended since they underrate dysphoric (hypo)mania, as the client does not feel his or her "best" despite having significant manic symptoms.

3. Note significant drug interactions that may be encountered during the treatment of persons with bipolar disorder may be found in Appendix A, Potential Drug Interactions.

A. Meets DSM-IV Criteria for Current or Past Major Depressive Episode (APA, 1994)

A(1). Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure.

Note: Do not include symptoms that are clearly due to a general medical condition or mood-incongruent delusions or hallucinations.

1(a). Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful). Note: In children and adolescents, can be irritable mood.

2(b). Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others).

3(c). Significant weight loss when not dieting or weight gain (e.g., a change of more than 5 percent of body weight in a month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains.

4(d). Insomnia or hypersomnia nearly every day.

5(e). Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).

6(f). Fatigue or loss of energy nearly every day.

7(g). Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).

8(h). Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).

9(i). Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

B(2). The symptoms do not meet criteria for a Mixed Episode (see p. 335 in DSM-IV).

C(3). The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

D(4). The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or general medical condition (e.g., hypothyroidism).

E(5). The symptoms are not better accounted for by bereavement, i.e., after the loss of a loved one; the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.

B. Meets DSM-IV Criteria for Current Cyclothymia (APA, 1994)

A(1). For at least 2 years, the presence of numerous periods with hypomanic symptoms and numerous periods with depressive symptoms that do not meet criteria for a major depressive episode. Note: In children and adolescents, the duration must be at least 1 year.

B(2). During the above 2-year period (1 year in children and adolescents), the person has not been without the symptoms in Criterion A for more than 2 months at a time.

C(3). No major depressive episode, manic episode, or mixed episode has been present during the first 2 years of the disturbance.

Note: After the initial 2 years (1 year in children and adolescents) of cyclothymic disorder, there may be superimposed manic or mixed episodes (in which case both bipolar I disorder and cyclothymic disorder may be diagnosed) or major depressive episodes (in which case both bipolar II disorder and cyclothymic disorder may be diagnosed).

D(4). The symptoms in Criterion A are not better accounted for by schizoaffective disorder and are not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or psychotic disorder not otherwise specified.

E(5). The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hyperthyroidism).

F(6). The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

C. Treat for Cyclothymia

Cyclothymia is a mild form of bipolar disorder, which can represent the prodromal phase of bipolar illness. The hallmark of cyclothymia is its biphasic nature characterized by marked changes in mood and behavior, for example, from lethargy and low self-esteem to high physical activity and overconfidence. Often, persons with cyclothymia are incorrectly diagnosed with an Axis II condition, such as borderline personality disorder. Family history is often helpful as an external validator for the diagnosis of cyclothymia, and any person with significant "mood swings" who has a clear family history of bipolar disorder should be considered part of the "bipolar spectrum" with respect to diagnosis and treatment.

Treatment of cyclothymia should emphasize close clinical follow-up in order to determine possible patterns of the mood swings, such as seasonal worsening. Clients should be encouraged to keep a diary or calendar to assist in diagnosis and in documenting results of treatment. In cases in which a client is distressed by the symptoms and/or where functional impairment occurs, cyclothymia should be treated as a bipolar disorder, with mood stabilizers as the first line of treatment. Tricyclic antidepressants have the potential to worsen the status of clients with cyclothymia and should be avoided. For depressive episodes that persist more than two weeks, a serotonin reuptake inhibitor antidepressant or bupropion may be beneficial (Akiskal 1994).

Care must be taken to not provoke mania, hypomania, mixed states, or rapid cycling by prescribing antidepressants without mood stabilizer coverage. Low doses of mood stabilizers may be effective in cyclothymia and may help to minimize adverse effects (Jacobson 1993).

D. Meets DSM-IV Criteria for Current or Past Manic/Hypomanic Episode (APA, 1994)

A(1). A distinct period of persistently elevated, expansive, or irritable mood, lasting through at least 4 days, that is clearly different from the usual nondepressed mood and is observable by others.

B(2). During this period of abnormal mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:

1. Inflated self-esteem or grandiosity
2. Decreased need for sleep
3. More talkative than usual or pressure to keep talking
4. Flight of ideas or subjective experience that thoughts are racing
5. Distractibility
6. Increase in goal-directed activity or psychomotor agitation
7. Excessive involvement in pleasurable activities that have a high potential for painful consequences
   
   These symptoms are not severe enough to cause marked impairment in social or occupational functioning or require hospitalization and have no psychotic features. Symptoms are not secondary to a substance or general medial condition.

A history of mania or hypomania will exclude a client from a diagnosis of major depressive episode, but clients presenting with depressive symptoms and such a history should be referred to a mental health professional because of the need for treatment and the risk that routine antidepressant medication might precipitate an unnecessary and potentially dangerous manic episode.

E. Person Rapid Cycler?

In DSM-IV, rapid cycling is defined as a course specifier for bipolar disorder as four or more affective episodes in 12 months. Episodes must meet full criteria for major depression, hypomania, mania, or mixed episode, and must be demarcated by 8 weeks of remission or by a switch to an episode of the opposite pole (e.g., depression to hypomania). Gottshalk et al. (1995) note that the pattern is not truly "cyclic," and its definition depends only on episode counting without reference to periodicity.

Clinically, briefer mood episodes ("truncated rapid cycling") are often seen in clinical practice; persons with this pattern are indistinguishable from those with rapid cycling in full episodes (Bauer et al. 1994). Those with full episodes may experience truncated episodes as well. Although not officially recognized in DSM-IV as rapid cycling, much has been done on samples that include both full-episode and truncated-episode rapid cycling subjects. Thus, logic dictates that in the absence of contrary evidence, those with truncated rapid cycling should be treated as those with full-episode rapid cycling.

Treatment strategies for DSM-IV-defined rapid cycling should also be used for truncated rapid cycling, in which episodes last for at least one day and are demarcated by switches to the opposite polarity or by remission of at least one day. However, since truncated rapid cycling ("ultra-rapid" cycling) can present diagnostic uncertainty in the absence of external validators such as family history, care should be exercised in entering these clients into standard clinical algorithms and treatment protocols.

F. Initiate Prophylaxis and Consider Psychosocial Rehabilitation

The goal of treatment for bipolar persons is complete remission of symptoms and a return to premorbid function. Bipolar disorder is an episodic, long-term illness with a variable course. Once the acute symptoms of a manic or depressive episode have been in remission for three to six months, a decision regarding further treatment will need to be made. The mean time between the first and second manic episodes may be about four years (Tohen et al. 1990a; Tohen et al. 1990b). In view of this and the large number of important developmental tasks (such as completing oneÌs education, establishing an occupation, and finding a significant other) facing young adults after the first episode, some clinicians may prefer to encourage clients who are uncomfortable with the idea of lifetime prophylaxis to at least agree to prophylaxis for several years. Long-term maintenance or prophylactic treatment is the rule rather than the exception for bipolar disorder. Clients should take an active role in this part of their treatment, since noncompliance is likely if the client does not understand and appreciate the need for prophylactic treatment. Most clients can be maintained for prophylaxis on mood stabilizers alone. Some data (Goodwin & Jamison 1990) suggest that prophylaxis is more successful if the dose of mood stabilizers and therapeutic blood levels are maintained at the level required for acute treatment. However, some persons can achieve adequate prophylaxis with lower doses and may prefer these, particularly if side effects are a problem.

Prophylactic treatment of a bipolar condition is complex. While many authorities recommend lifetime medication, many clients have difficulty accepting this, at least initially. In clients with frequent and severe episodes that have responded dramatically to medication, prophylactic treatment should be prescribed indefinitely. Persons with an acute manic episode should be treated at least for six months after the initial episode is controlled, and encouraged to continue on life-long prophylactic treatment. For most persons with more than one manic episode, or with one manic and one depressive episode, or three or more depressive episodes, the benefits of prophylaxis clearly outweigh the risks.

There are no controlled data on when to begin long-term mood stabilizer therapy, whether after the first manic episode, the second affective episode, or later. Of persons who recovered from an initial manic episode, between 25 and 50 percent did not have a recurrence during long-term follow-up of 2 to 30 years, and of those who relapsed and then recovered from a second episode, 45 percent remained well at 3 years of follow-up (Lundqvist 1945; Bland & Orn 1982). These studies provide some data that may be used to convey risks to clients after recovery from the first or second manic episodes. Zarin and Pass (1987) used a creative decision-analytic approach to assess the tradeoffs between long-term prophylaxis of the first manic episode versus delayed treatment. While their specific findings are difficult to apply to the individual case, they succinctly convey the logic that "Earlier use of lithium increases the benefits (morbidity avoided) and increases the costs (lithium-associated morbidity). The decision therefore involves choosing an acceptable tradeoff between different types of morbidity" (Zarin & Pass 1986). Thus, the clinician should explain these considerations to the client in deciding on long-term prophylaxis.

In a minority of cases where a person has a clear history of long periods between episodes, long-term prophylaxis with a mood stabilizer may not be required, particularly if the person and family are educated and aware of subtle, early symptomatology of the disease and are involved in the follow-up (Goodwin & Jamison 1990). However, concerns about covert disease progression and emergence of medication resistance ought to be discussed with client and family.

In general, the mood stabilizing medication(s) used for the control of the index episode can be used for the continuation and prophylactic phases. Lithium has the strongest evidence for efficacy in prophylaxis. There is limited evidence for the efficacy of carbamazepine in the maintenance phase. There are no published data on controlled trials of valproate in the maintenance phase, but open trials indicate efficacy. ECT can be used as a maintenance treatment if there is a reason not to use the mood stabilizing medications (Frances et al. 1996).

The importance of regular client follow-up for the maintenance or prophylactic phase of treatment cannot be overemphasized. Clients should been seen in clinic every 1 to 3 months, with blood levels of mood stabilizers monitored at least every six months. Also, tests for thyroid, kidney, and liver function should be done every 1 to 2 years. Clinically triggered assessments of drug levels (due to a change in mood or adverse effects) and chemistries (due to physical adverse effects) are crucial.

If agents are discontinued due to the desire to conceive, tapering done in conjunction with gynecological supervision is advised in an effort to help the woman to conceive as quickly as possible. A medication-free state during a period of illness remission may minimize medication-free time during pregnancy. However, in view of the high risk of postpartum relapse (Cohen et al. 1995), medications ought to be started as soon as possible after delivery.

If a client and/or physician elect to discontinue mood stabilizer medication, a very slow and gradual taper schedule should be used, since there are some data (Baldessarini et al. 1996; Faedda et al. 1993) stating that an episode of bipolar disorder may occur sooner in clients who stop mood stabilizers abruptly. The dose of mood stabilizer should be tapered for at least a 2 to 4 week period (or longer if needed).

Experimental and naturalistic data on the impact of discontinuation of lithium treatment can help the clinician who is faced with deciding whether to continue mood stabilizers. This issue arises in general clinical practice for a number of reasons, including intolerable side effects, desire for pregnancy, intercurrent illness, client preference, or nonresponse to treatment. Several studies are briefly reviewed.

Suppes et al. (1991) compiled data from 124 bipolar type I persons in 10 studies who were stable for an average of at least 30 months prior to lithium discontinuation. Fifty percent of clients relapsed within 5 months of discontinuation, and half of these relapsed within 6 weeks. Among those who relapsed, mania occurred more often than depression, and significantly earlier (2.7 versus 14 months). The time to relapse after discontinuation was shorter than the prior illness pattern would have predicted, suggesting that lithium discontinuation may have caused a physiological "stress" to otherwise stable persons. Suppes et al. (1993) reviewed another 15 studies of 632 clients with mood disorders and determined that relapse rates were almost threefold higher after lithium discontinuation (75 percent versus 27 percent). Faedda et al. (1993) compared rapid (< 2 weeks) versus slower (2 to 4 weeks) lithium discontinuation in a prospective naturalistic study of 64 bipolar type I or II clients stable for an average of 3.6 years. Rapid discontinuation resulted in more and earlier relapses. Bouman et al. (1986) found earlier and more frequent relapses in bipolar or schizoaffective clients after lithium was discontinued during lithium treatment. Mortality from suicide and from other medical causes (Muller-Oerlinghausen et al. 1992; Nilsson 1995) appears to be higher in such clients. In summary, clients who are sufficiently ill to be placed on lithium may expect increased morbidity (and perhaps mortality) when lithium is discontinued. Also, up to 20 percent of persons for whom lithium is discontinued respond less well to lithium if it is later reinstituted (Maj et al. 1995). Although there are no data regarding other mood stabilizers, similar concerns apply, and similar procedures should be followed.

Thus, persons with clearly defined bipolar disorder type I who have achieved extended stability should be continued indefinitely on mood stabilizer treatment unless there are clear medical or personal reasons for discontinuation. Similar logic, though less evidence, applies to those with bipolar disorder type II and schizoaffective disorder. In persons who are stable and for whom mood stabilizer discontinuation is being considered, careful cost-benefit analysis (Current Manic/Hypomanic/Mixed Episode Module E, annotation C) must be undertaken. A slow taper, over at least 2 to 4 weeks, is recommended, unless medically contraindicated.

Prophylaxis for Subsyndromal Symptoms in Bipolar Disorder

Clients may present to clinic with mild chronic depression (dysthymia) or mild chronic hypomania (hyperthymia), which may be the first symptom of an underlying bipolar disorder that has not yet evolved into definite mania or depression. In these cases, the client may not meet criteria for bipolar disorder, but may be considered to have subsyndromal mood disorder. Where the diagnosis is not clear, a positive family history of mood disorder can provide an important external validator for the diagnosis.

Regular clinical follow-up is particularly important to document improvement or worsening of symptoms. If symptoms persist or worsen, e.g., insomnia, the person may need pharmacologic treatment. Other symptoms, such as impulsivity or risk taking, may respond to focused psychotherapy. A trial of mood stabilizer for subsyndromal mood disorder may be elected by client and clinician.

Clients with subsyndromal bipolar disorder should have closely monitored blood levels of mood stabilizers and may respond to an increase in dosage of medication. For example, some persons may have subsyndromal symptoms at lithium levels of 0.5 mEq/L, but be essentially nonsymptomatic at levels of 0.8 mEq/L. Clients who have previously responded to treatment and been completely nonsymptomatic for several months or years who then develop subsyndromal bipolar disorder should be followed closely and treated aggressively, since the subsyndromal state may be a precursor of another manic or depressive episode. Mood stabilizers should be optimized and supplemental medications used as indicated.

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