Bipolar Depression in Primary Care

Major depressio n is commo nly see n in primary care practice. Several studies have indicated that 25-40% of primary care patients who experience an episode of major depression in fact have bipolar depression. Depression is by far the predominate mood state in bipolar disorder, encompassing 32-50% of all patient weeks in long-term naturalistic studies. Failure to differentiate bipolar from non-bipolar depression often leads to multiple failed trials with combinations of antidepressants. It is well-documented that antidepressant monotherapy may trigger destabilization of the illness, inducing acute mania, rapid cycling, or a mixed bipolar episode, with an associated increased risk of suicide. Therefore, bipolar depression must be considered in the differential diagnosis of all patients with depressive and anxious symptoms. A bipolar screening instrument, such as the Mood Disorder Questionnaire (MDQ; available for download at www.psycheducation.org/PCP/launch/MDQlaunch.htm), should be routinely utilized. Physicians must also look for the “clinical picture” that suggests bipolar disorder in depressed patients.

Management of patients with bipolar depression

The cornerstone of successful treatment of bipolar depression is the therapeutic alliance between the patient and their physician (and often family as well). An optimal outcome can only be achieved when the patient and physician are in agreement (concordance) with the diagnosis and treatment plan. All patients must be provided with sufficient education about their illness to participate in their care and “believe” in the benefits of their treatment. The practical management techniques discussed below can not only optimize care, but can have the added benefit of enhancing patients’ insight into their illness, and therefore involvement in their care.

Ideally, primary care physicians should strive to establish a referral and co-management relationship with a trusted psychiatrist, who can assist with patients who are very ill or fail to respond to initial treatment. Unfortunately, psychiatric consultation is not readily available in many areas of the country. Other obstacles, including patient resistance and lack of adequate mental health insurance coverage, further obstruct obtaining psychiatric consultation. Primary care physicians who treat patients for depression can become comfortable treating bipolar depression as well. Once the diagnosis has been established, effective FDA-approved treatments are available. I have found that discovering the true nature of a patient’s continual or recurrent depression, and prescribing the correct medication that finally gets them well, is one of the most rewarding aspects of my family practice. Patients under treatment for bipolar depression require frequent and systematic follow-up. At each visit, the patient must be assessed for current symptoms of depression and mania, which can be accomplished in an accurate and time-efficient manner by the use of patient-rated mood questionnaires.

Readily available tools such as the PHQ-9 or Zung Depression Scale are adaptable to assess depression symptoms every visit. The consistent use of these tools will allow the physician to obtain and document the maximum amount of information in the limited time available in today’s primary care practice. The use of such scales allows the physician to objectively track treatment response and to identify residual subsyndromal symptoms of both mood poles. Patients with bipolar depression need to be queried about concurrent manic symptoms. I like to use the mnemonic “I DIG FAST” to prompt me to ask my patients about the following symptoms at every visit: Irritability, Distractibility, Insomnia (decreased need for sleep), Grandiosity, Flight of ideas (racing thoughts), Activity (increase in goal directed activity or psychomotor) Agitation, increase in Speech, and Thoughtlessness (risk taking, spending sprees, impulsive behaviors).

Daily mood charting is an important tool in the management of bipolar disorder. Mood charting helps patients to become aware of subtle changes in mood, energy, and sleep that may signal an impending relapse, as well as identify brief episodes of depression or hypomania that may otherwise go undetected during office visits. Mood charting provides an expanded view of responses to medication changes over time, and helps patients correlate stressful life events or behaviors with changes in their mood, reinforcing healthy lifestyle choices in order to remain well. An excellent mood chart, with instructions, is available for download at www.manicdepressive.org/moodchart.html. Patients with bipolar disorder are prone to mood relapses and tumultuous lives. A missed or cancelled appointment without one rescheduled can be a sign of a relapse. Physicians should develop a protocol to contact patients who have failed follow-up. Family members should be involved in this process when appropriate. This underscores the need to use evidence-based treatment strategies that afford rapid control of bipolar depression with complete and sustained remission as the goal.

Treatment of bipolar depression

Given the severe difficulty bipolar depressed patients experience in their lives, I find it very useful at the initial diagnostic visit to ascertain the three (or more) critical symptoms from which the patient most desperately seeks relief. I make sure that I target these symptoms in the initial treatment options that I discuss with the patient, (as well as symptoms I feel require urgent intervention). This reassures the patient that I have listened and care about what bothers them the most. It is also important to firmly establish the expected benefits of treatment, so the patient can have the proper perspective when evaluating the benefits and possible side effects associated with various medication options. My primary treatment goal is the rapid stabilization and improvement of the patient’s most urgent psychiatric symptoms.

Currently, there are two FDA-approved medications for bipolar depression. Expert consensus treatment guidelines have been published that can guide evidence-based alternatives when approved treatments are not fully effective or not tolerated. Available guidelines include the Texas Implementation of Medication Algorithms (TIMA) Guidelines for Treating Major Depressive Disorder (available online at www.dshs.state.tx.us/mhprograms/timaMDDman.pdf) and the practice guidelines developed by the American Psychiatric Association (the full collection is available online at www.psych.org/MainMenu/PsychiatricPractice/PracticeGuidelines_1.aspx).

Adverse Events (Side Effects)

It is essential that physicians utilize the most effective, evidence-based treatment for the bipolar depressed patient. Simultaneously, physicians must provide the patient with strategies to ameliorate potential adverse events from the prescribed medication in order to achieve compliance with the treatment regime. The most common adverse events that occur with approved treatments for Bipolar Disorder are sedation and “metabolic” side effects such as weight gain, dyslipidemia, and impaired glucose metabolism. My experience is that with appropriate guidance, most potential side effects can be avoided or effectively managed.

Sedation attributable to these treatments is dose-related and transitory, with most patients accommodating to bothersome sedation in the first several days of treatment. Informing patients of the transient nature of daytime grogginess encourages them to continue treatment through this accommodation period. Often, dosing earlier in the evening (rather than at bedtime) will minimize morning sedation. Treatments with more rapid onset of action are best given at bedtime, and titrated to the target dose over four to seven nights. Nearly 25% of patients with bipolar depression who participated in clinical trials involving the two FDA-approved treatments for bipolar depression experienced significant weight gain. Thus, physicians should implement proactive interventions to ameliorate the effects of appetite increase to prevent substantial weight gain and improve long-term adherence with treatment.

Patients should be informed that they may experience an increase in appetite, specifically carbohydrate craving. I always discuss with my patients the four key elements of preventing weight gain: (1) reducing intake of refined carbohydrates (“If it’s white, don’t bite!”); (2) not drinking high-calorie beverages; (3) increasing intake of lean protein (eg, foods that had “fins or feathers”); and (4) walking at least 20 minutes per day.

I encourage liberal amounts of non-starchy vegetables throughout the day. Finally, I ask patients to identify one or two high-calorie food they can decrease in their diet (eg, ice cream, oil-based salad dressings, cheese, nuts). There are many websites and books that provide concrete guidance for patients wishing to follow a high-protein, low-carbohydrate, and low-fat eating strategy. In my experience, patients who will follow these dietary guidelines are seldom challenged with bothersome weight gain. Other non-pharmacological interventions to avoid substantial weight gain include formal nutritional and exercise programs, counseling, and programs such as Solutions for Wellness. Some patients may be appropriate for a medically-based bariatric weightloss program, with a referral to a bariatric physician subspecialist.

(See www.asbp.org for a list of board-certified bariatric specialists). In my experience, the combination of lifestyle and dietary modifications has allowed most of my patients who have experienced initial weight gain to continue with the most effective treatment for their bipolar illness. Pharmacological interventions aimed at reducing treatment-emergent appetite increases and weight gain in psychiatric patients have not been systematically studied. Currently there are no FDA-approved adjuvant treatments to ameliorate weight increase in bipolar patients. In my experience, an understanding and supportive bedside manner, combined with aggressive diet and lifestyle intervention, has allowed most of my patients who have experienced initial weight gain to continue with the most effective treatment for their bipolar depression.

Monitoring and managing risk factors

There is growing evidence that patients with bipolar disorder have a high prevalence of key cardiovascular risk factors and significantly higher mortality rates from cardiovascular and cerebral vascular disease (1.7 and 1.6 fold) and smoking-related lung disease (2.4 fold) compared with the same aged non-bipolar population. In one study of 170 bipolar patients, 30% were found to meet NCEPEP criteria for metabolic syndrome. 49% of these patients had abdominal obesity, 41-48% had dyslipidemia, 39% were hypertensive, and 8% had elevated fasting glucose levels. Furthermore, up to two-thirds of bipolar patients are addicted to cigarette smoking. Therefore, all bipolar patients should be assessed for these modifiable risk factors initially and throughout treatment. Guidelines regarding monitoring metabolic changes in patients treated with AAPs have been published by the American Diabetes Association. Strategies to reduce these risk factors, including efforts to reduce cigarette smoking, are an essential part of the comprehensive treatment of patients with bipolar disorder.

Patients should be asked about signs and symptoms of elevated blood glucoses at follow-up visits, and their weight and blood pressure should be measured every visit. Random finger-stick glucose determinations at follow-up visits can be helpful in patients at risk. Patients with random blood glucoses above 140 mg/dl should have fasting studies.

Effective treatment

My first priority is the urgent stabilization and symptom improvement of my patients with bipolar depression, but the risks of the selected treatment must be weighed as well. A critical decision point arises when a patient has experienced marked improvement in their depression with a certain medication, but is now experiencing worsening in the aforementioned metabolic parameters. A “risk vs. benefit” analysis and discussion with the patient must then take place. Many patients will want to continue the medication that effectively treated their depression, and they should be offered specific pharmacologic treatment directed toward the metabolic abnormality. Once remission is obtained, consideration might also be given to instituting an approved bipolar maintenance medication that may have less metabolic effects and still maintain their remission. Today, patients with bipolar disorder have effective treatments available for their depression that can assist them in leading rewarding and productive lives. With the combination of a strong therapeutic alliance, patient education, vigilant monitoring for mood changes and adverse events, with early intervention utilizing the strategies discussed above, most of our bipolar depressed patients can safely remain on the most effective treatment.

Peter J. Knoblich, MD, is a diplomate of the American Board of Family Practice who specializes in the treatment of mood disorders at his private practice in northern California.