Anxiety and Bipolar Disorder
by M. Katherine Shear, M.D., Associate Professor of Psychiatry, University of Pittsburgh, Director, Anxiety Disorders Clinic.
Anxiety is a normal part of everyday life. Anxiety acts as a signal which motivates us to improve performance and alerts us to impending dangers. Yet anxiety can get out of hand. When this happens, the normal warning signal mechanism of anxiety becomes a psychiatric symptom.
Anxiety symptoms occur in a group of disorders characterized by "free-floating" anxiety (panic disorder and generalized anxiety disorder), phobic anxiety (specific and social phobia), traumatic anxiety (posttraumatic stress disorder and acute stress disorder) and obsessive compulsive symptoms. Each of these disorders includes features of symptomatic anxiety, such as high levels of bodily arousal, excessive worries about potential danger, and avoidance of feared situations.
The disorders differ in the degree of preoccupation with body symptoms, the focus of worry and the extent and type of avoidance. Many clinicians and most consumers and their families are unfamiliar with the differences between these diagnoses and tend to view anxiety as a general and overall symptom. This is particularly true when an anxiety disorder occurs along with another illness, and when the latter illness is the focus of treatment. Nevertheless, the different anxiety disorders have different ways of working in the body and also have different responses to different kinds of treatment. The purpose of this article is to help clinicians, consumers and their families to be aware of the clinical significance of anxiety disorders when they occur in people with bipolar illness.
Anxiety disorders are the most common psychiatric conditions in the community. These disorders are often trivialized, in part because of their high frequency and in part because anxiety is a normal part of life. However, anxiety can become debilitating. Anxiety disorders have been shown to cause difficulty in people' s ability to function in their daily lives and can affect quality of life as well. Experiencing a major depression greatly increases the likelihood of having an anxiety disorder. When an anxiety disorder is also present, depression is more severe and is more likely to fail to respond to treatment. The presence of panic attacks increases substantially the risk of suicide in a depressed individual. Other debilitating anxiety disorders, including social phobia, obsessive compulsive disorder, and posttraumatic stress disorder, are also commonly seen with depression.
Anxiety disorders appear to be common in people with bipolar disorder as well, yet anxiety is rarely discussed in the medical literature on bipolar illness. Clinicians and people with bipolar disorder may well be unaware of the potential very negative consequences of this seemingly unimportant complication. Most of the existing literature focuses on panic disorder and obsessive compulsive disorder (OCD), both of which are greatly elevated in bipolar illness. For example, in the recent Epidemiologic Catchment Area study, it was found that 21% of people with bipolar disorder and 12.2% of people with unipolar depression had also experienced OCD at some time in their lives. People with bipolar disorder were two times more likely than people with unipolar depression to develop OCD and were more than three times more likely to develop OCD than people without either bipolar or unipolar disorder. These data suggested not only that OCD is relatively common in bipolar illness, but that OCD in people with bipolar disorder also may be associated with panic disorder.
Another study found that 20.8% of people with bipolar disorder experienced panic disorder at some time in their lives compared to 10.0% of people with unipolar depression and 0.8% of people without mood disorders. People with bipolar disorder were 19 times more likely than people with no mood disorder to develop a panic disorder and were almost two times more likely to develop panic disorder than people with unipolar depression. In another study of 26 "pure manic" patients and 15 "depressive manic" patients, panic disorder was significantly more likely to occur in the latter-80% versus 23%. Two people in this study failed to respond to treatment and required long term institutionalization. Both were "depressive manic" patients who also had panic disorder. All 7 suicidal patients in this study were "depressive manic" patients who also had panic disorder.
What is known about how anxiety exerts its negative effects in people with bipolar disorder? One study looked at differences in how individuals with bipolar disorder reacted to stress. These investigators found that people who scored high on tests of introversion and obsessionality tended to relapse more often than people with low scores on these same tests. The personality traits of introversion and obsessionality have been shown in other studies to be strongly associated with anxiety disorders. It may be that early onset of anxiety contributes to the development of these personality characteristics. Posttraumatic stress disorder and social phobia [fear and avoidance of social performance situations in which the individual is exposed to evaluation by others or in which embarrassment may occur] have not been studied in bipolar illness, but it is likely that these also occur with elevated frequency and with negative consequences. People with bipolar disorder may have traumatic experiences during manic episodes, and for some people the manic episode itself may be experienced as a trauma. Social phobic symptoms may be of special concern during depressive episodes. People with bipolar disorder may also have problems with substance abuse; we know that the use of alcohol and of other recreational drugs is associated with anxiety disorders. Panic attacks and anxiety occur frequently during alcohol and sedative withdrawal states. Withdrawal also can worsen an underlying anxiety disorder. Some people develop panic disorder during cocaine use, and the panic attacks persist for years after cocaine use has stopped. More work in this area is clearly needed.
Other studies show that family members of people with bipolar disorder have a higher rate of anxiety disorders and of personality traits (such as compulsive personality) associated with anxiety disorders. In a recent study, people with bipolar disorder who had high levels of anxiety were more likely to engage in suicidal behavior than people with bipolar disorder who did not experience anxiety (44% vs. 19%). The same held true for alcohol abuse (28% vs. 6%), cyclothymia (44% vs. 21%) and an anxiety disorder (56% vs. 25%). There was also a trend toward lithium nonresponsiveness in people who had both bipolar disorder and high anxiety. In addition, the diagnosis of an anxiety disorder was related to low scores on a measure of daily life functioning.
These findings suggest that having an untreated anxiety disorder in bipolar illness has negative implications; similar negative implications have been repeatedly demonstrated in unipolar depression. Though not directly studied as yet, identification and treatment of anxiety disorders in people with bipolar disorder are likely to have important beneficial effects. If anxiety disorders are common in people with bipolar disorder and tend to predict poor outcome, what can be done to treat these disorders? Fortunately, there has been considerable progress over the past few decades in the treatment of anxiety disorders. Most people with these disorders can be treated with effective medication therapies and/or a specific kind of psychotherapy called cognitive behavioral therapy. The next [part of this article] will include information about the current standard approaches to treatment of anxiety disorders and more details about available treatment strategies.
There are no treatment studies that specifically address the needs of people who suffer from both of these illnesses at the same time. In this article, we will review current recommended treatment strategies for several different kinds of anxiety disorders (uncomplicated panic, OCD, PTSD, and social phobia, all of which were defined [above]). We hope this information may be useful to people with bipolar disorder and their family members.
Several types of medication are helpful in treating panic disorder. These include some of the antianxiety medications (high potency benzodiazepines such as Xanax [alprazolam] and Klonopin [clonazepam]) and some anticonvulsants in addition to several different classes of antidepressants. Antidepressants which have been helpful include medications which are active in the serotonin system in the brain, called SSRIs, such as Paxil [paroxetine], Zoloft [sertraline], Prozac [fluoxetine], and Luvox [fluvoxamine], tricyclic antidepressants (TCAs) that influence serotonin (such as Tofranil [imipramine] and Anafranil [clomipramine]), and the MAO inhibitors (Nardil [phenelzine] and Parnate [tranylcypromine]).
The general strategy for treating panic disorder is to begin with an extremely low dose and raise it gradually until a therapeutic level is achieved. One study suggests that treatment of people who have both bipolar disorder and panic disorder is best accomplished using Klonopin [clonazepam], another benzodiazepine, or possibly an anticonvulsant. These authors recommend avoiding TCAs, SSRIs, and MAO inhibitors if possible, because of the risk of precipitating a manic episode with the antidepressant medications.
Cognitive behavioral therapy (CBT) is also effective in treating panic disorder. Panic control treatment is a specific treatment intervention that has been outlined in a series of treatment manuals (Barlow and Craske, 1994). The treatment has four parts. First, education/ information about panic is stressed, including correction of common misconceptions about what panic is and what it means. Next breathing retraining, a slow abdominal breathing technique with a meditation component, is taught. This is followed by training in cognitive restructuring, which involves focusing on changing the negative ideas or expectations that people have about what will happen to them when they are panicky and also on decreasing the fears that they have about what will happen to them physically as a result of becoming anxious. For example, a person prone to panic will often experience harmless physical sensations, like a heart palpitation, and be firmly convinced that they are symptoms of a serious medical problem, like a heart attack. Cognitive restructuring helps the person to recognize and to learn to challenge the negative beliefs and fears about physical sensations that are so firmly held. In the final phase of the treatment, the person actually experiences the sensations that are frightening him or her in a controlled situation and challenges the fears and negative thoughts. This process breaks the link between the physical sensation and the fear reaction and blocks panic attacks. Although there are no published studies of the use of this treatment for people who have bipolar disorder and panic attacks, people with psychotic disorders and panic attacks have been successfully treated.
Recent work by our group, as part of a four-site multicenter collaborative study, confirms the fact that both pharmacotherapy [treatment using medications alone] and cognitive behavioral approaches have yielded very good treatment outcomes which are approximately equivalent. For people with uncomplicated panic attacks [those with no or very little phobic avoidance of feared situations], the combination of both pharmacotherapy and cognitive behavioral therapy does not appear to add further benefit. However, for people whose illness is complicated or has not responded well to other treatments, a combination of both these treatments may be best. For patients who have moderate to severe agoraphobia [difficulty being in situations where help may not be available or where escape might be impossible, which for many people means difficulty being away from home, especially if one is alone], there is also some suggestion in the literature that combination treatment with medications and cognitive behavior therapy may be best. In any case, if medications are used, it is very important to also encourage the ill person to confront and learn how to manage feared situations.
Obsessive Compulsive Disorder
OCD can be treated successfully using either behavioral treatment or medication. Again, little research has been done on the treatment of OCD when it occurs along with bipolar illness, so what follows is a summary of current clinical thinking about treating OCD in general. Serotonin-active medications seem to be most helpful in treating OCD. Antidepressants without serotonin activity are of no use at all; they show results similar to placebo in clinical trials. Anafranil [clomipramine] was the first antidepressant medication approved for the treatment of OCD, and it is quite effective. However, current recommendations are to begin treatment with a more selective serotonin medication, such as Paxil [paroxetine], because there are fewer side effects. Of course, people who have bipolar disorder and take antidepressant medication also need to be taking a mood stabilizing medication to lower the risk of triggering a manic episode.
Behavior therapy can be at least as effective as medication in the treatment of OCD. Behavior therapy must be administered by a trained therapist. It requires the specific interventions of exposure and response prevention. That is, the person who is coming for treatment is both exposed to the situation that triggers the OCD symptoms and also asked to respond differently afterward, that is, not repeat the behaviors that he or she has used in the past to cope with the anxiety. First, the situations which provoke anxiety and compulsive rituals for that person must be identified (such as using the bathroom, or touching an ordinary household object considered to be "contaminated"). The person is then asked to perform the activity (use the bathroom, touch the object) and to refrain from washing afterward. This exercise is often very difficult for a person who has OCD, and so it requires the skillful support of a trained therapist. When people who suffer from OCD are able to allow themselves to participate in behavioral treatment, it is usually highly effective. When behavior therapy is the treatment employed, adding medication appears to add little to treatment response. However, when medication is the treatment of choice, adding behavior therapy may improve the treatment response. People taking medication for OCD who are able to confront situations which have led to compulsive behaviors or rituals generally do better than those who avoid these situations, and this is especially true if the urge to do the ritual behavior can be resisted. Therefore, as with panic disorder, doctors using medication to treat people who have OCD should also encourage exposure and response prevention.
Social phobia has been less well studied than other anxiety disorders in bipolar illness. Social phobia is more likely to occur during a depressive episode, while panic and OCD may occur at any time. The best studied medication for uncomplicated social phobia is the antidepressant Nardil [phenelzine], an MAO inhibitor. High potency benzodiazepines, such as Klonopin [clonazepam], have also been shown to be effective. SSRIs are currently under investigation, and preliminary studies indicate that they also may be useful. Since clonazepam generally is not recommended as treatment for people suffering with severe depression, an MAOI or SSRI may be the treatment of choice for people with bipolar illness. And as with OCD and panic disorder, people with bipolar disorder and OCD who are taking antidepressants also should be taking mood stabilizers like lithium or anticonvulsants.
Cognitive behavioral therapy for social phobia is also effective. The best studied approach is group cognitive behavioral therapy. In a study comparing two types of group treatment, group cognitive behavioral therapy worked significantly better than a supportive group treatment. Similar to the treatment for other anxiety disorders, the group cognitive behavioral approach requires exposure to anxiety provoking situations, with a change in the person' s usual behavioral response (which is generally some sort of escape behavior). Social skills training is sometimes incorporated. The combination of CBT and medication for social phobia has not been studied, but it is likely to be helpful, especially for individuals whose illness does not respond to medication or CBT alone. Again, encouragement regarding exposure to feared social situations should be a routine part of treatment with medication.
Post-Traumatic Stress Disorder
PTSD is a recently recognized condition which may be much more common than was once thought. The symptoms of PTSD occur after a person has been exposed to a situation in which there has been a direct and serious threat to the person' s life or body, or has witnessed a similar threat to another person. The individual experiencing or observing this situation feels a sense of intense horror and helplessness, followed by symptoms of re-experiencing the trauma in nightmares, flashbacks, memories, etc. A person who develops PTSD generally avoids reminders of the threatening situation. He or she may develop full-blown agoraphobia, may withdraw from other people, and may expect that the future will not hold much and that life will not last long. Also common are feeling emotionally numb and unresponsive to others after the incident. People also experience symptoms of increased arousal, such as startling easily, insomnia, difficulty concentrating and hypervigilance [scanning one' s immediate area and trying to remain aware at all times of what is happening around one]. PTSD has not been well studied in bipolar illness. However, since people with bipolar disorder often engage in risky behaviors when they are ill, it is likely that they may be exposed to life threatening situations and that PTSD may also occur. Medication treatments for PTSD are less well developed than that for other anxiety disorders. Serotonin-active medications are often used but are not yet well studied. Other medications that have sometimes been helpful include tricyclic antidepressants, MAO inhibitors, anticonvulsants, anti-adrenergics (beta blockers like Inderal [propanolol]) and drugs that block the receiver side of the space between neurons, such as Catapres [clonidine] and the benzodiazepines.
Behavior therapy for PTSD has been well-studied and appears to be effective. In particular, rape survivors whose treatment involves exposure to the memories of the rape experience respond with considerable relief of symptoms. Therapists working with people who have PTSD allow the person the opportunity to describe the trauma and periodically invite the person to re-tell this story. Even a limited number of such opportunities can be quite therapeutic, but this treatment should be administered following specified procedures and only by trained therapists or re-traumatization of the survivor can occur.
Summary and Conclusions
Anxiety disorders occur frequently. They are disabling conditions which often occur in addition to other illnesses. In particular, people with bipolar disorder also commonly have anxiety disorders, and when anxiety disorders are present, they may complicate treatment for bipolar disorder. Studies have shown that the co-occurrence of anxiety and mood disorders regularly leads to a poorer outcome. Therefore, it makes sense for clinicians treating people with bipolar disorder to attend to the possibility of the presence of a co-occurring anxiety disorder and to administer treatments known to be helpful for the specific anxiety disorder involved. Often pharmacological treatments (antidepressants, clonazepam and anticonvulsants) are similar to those already in use for treating the symptoms of bipolar disorder. However, the recommended starting doses and strategy for increasing medication may differ depending on which illness or illnesses are being treated. The presence of a clinically significant anxiety disorder may be a reason for adding clonazepam or other benzodiazepines, which otherwise would not be chosen.
Behavioral treatments are highly effective for all anxiety disorders and should be considered for people who have both bipolar disorder and anxiety disorders, especially for those still experiencing symptoms despite receiving adequate medication. In terms of non-pharmacological therapy, the general therapeutic principle of exposure to the feared situation holds for all these treatments. It is important that an adequate rationale for such exposure be presented so that the person with bipolar disorder and his or her family members understand its importance. A detailed presentation of exposure rationale is beyond the scope of this brief review. However, such descriptions can be found in the literature and are well known by trained behavior therapists.
Barlow DH, Craske M, Mastery of your anxiety and panic. Psychological Corporation, San Antonio, TX, 1994.
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This article was originally published in two parts in Stanley Center Innovations for Particpants (Spring and Fall, 1997) and is reprinted with permission.