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Schizophrenia Information > An Introduction to

Bipolar Disorder Q and A with Dr. Terence Ketter

Stanford Schizophrenia and Bipolar Education Day, July 30 2005

Questions Index (divided by subject category):

Bipolar onset, causes, and diagnosis:

Medication questions:

Treating symptoms of bipolar mania and depression

Long-term considerations, remission, and recovery

Editor's Note: the following is a summary of the question-and-answer session on bipolar disorder, hosted by Stanford Associate Professor of Psychiatry and Chief of the Bipolar Disorders Clinic Dr. Terence Ketter. Direct quotes are indicated by quotation marks; any other text is paraphrase based on Dr. Ketter's words.

Q: How often does a "John Nash" type of remission (i.e., total disappearance of visible symptoms and a return to a normal life) happen for people with bipolar disorder?

A: The definition "Remission" in bipolar means a return to the level of mood symptoms seen in the general population. A limitation to this definition is that it does not include functionality level.

In the majority of cases, symptoms will be brought under control. "For any given episode, the prognosis of that episode being over is extremely can almost count on it." More challenging is decreasing the number of total episodes, and regaining previous function - that is, how long does it take before the person can do what they used to do before they got sick. According to Dr. Ketter (based on his clinical experience), It can take months or years after a remission of symptoms to build back previous function.
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Q: How do the medications for bipolar disorder affect the creativity and productivity of a bipolar person?

A: According to data from Stanford Bipolar Disorder Clinic studies, mood stabilizers do not appear to impair the original creativity level of a person with bipolar before they started medication. When comparing four groups of subjects - bipolar disorder subjects in remission, unipolar subjects in remission, healthy controls, and "creative controls" (people involved in fine arts, product design, and writing graduate studies at Stanford University). On one particular "creativity scale" (the Barron-Welsh Arts Scale), the bipolar subjects consistently scored higher than the healthy controls and the creative controls, whether or not they were taking medication. According to Dr. Ketter, about 1/4 of the bipolar subjects were not taking medication at the time of the study.

One interesting finding - although it was not statistically significant - is that people with bipolar who were not taking lithium scored a little higher on the BWAS than people who were. Some studies of lithium have indicated that at very high doses (for example, a blood level of above 0.8), it can affect creativity due to a general emotional blunting.

"If we're doing our job right", said Dr. Ketter, "we shouldn't be messing up the ability to be creative and produce. We shouldn't be flattening affect so much that people can't have any passion or any associated energy."

For more on the association between creativity and mood disorders, Dr. Ketter recommended Dr. Kay Jamison's book "Touched With Fire"
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Q: How do you deal with paranoia in bipolar disorder - is it completely treated with medications, or are there things that family and friends can do to help reduce paranoia symptoms?

A: What is very common with people who are manic is to have paranoid delusions (although it can occur in depression as well), and most paranoid delusions will go away with medication treatment. The standard medication treatment for paranoia is to stablize mood with a mood stabilizer or an atypical antipsychotic. Paranoid delusions are technically considered a psychotic symptom.

(Editor's note: for more tips, see 6 steps for dealing with paranoia)

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Q: What is the long-term prognosis for rapid-cyclers vs. non-rapid-cyclers? Are rapid cyclers harder to stabilize?

A: Rapid-cyclers (clinically defined as four or more episodes per year) constitute a subset of bipolar disorder, and are generally considered more challenging to treat.

There are two ways to look at bipolar disorder - one is how fast the person is cycling, and the other is how severely they are cycling (how extreme the highs and lows are). People with bipolar I have severe mood elevations (manias), which can be manifested through psychotic symptoms, hospitalization, or a catastrophe/crisis. For people with bipolar II, generally the manias are not as severe (in fact, they are called hypomanias rather than manias).

The two types of bipolar disorder carry different burdens. Bipolar II tends to have a higher burden of depression, while bipolar I has a higher tendency to antidepressant intolerance. Both tend to spend more time in depressive episodes, but the ratio is much higher for bipolar II than bipolar I. According to one study, the ratio of time spent in depressions as opposed to manias is about 2:1 for bipolar I subjects; for bipolar II subjects, the ratio can be more like 20:1.

Rapid-cycling makes bipolar II worse by also increasing the antidepressant intolerance (someone with rapid-cycling bipolar II will be more likely to switch to a mania/hypomania if treated with antidepressants, according to data collected by following 1000 patients for 18 months). For bipolar I, the switch rate on antidepressant was about 1 in every 5 episodes, as compared to about 1 in every 10 for non-rapid cycling bipolar II subjects.

Rapid-cyclng, therefore, appears to be a depressive subtype of bipolar disorder.
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Q: What is the link between substance abuse and bipolar disorder?

A: Bipolar disorder is the Axis-I diagnosis most often associated with a history of substance abuse, even more so than schizophrenia. In some studies, 60% of people with bipolar disorder have a lifetime history of substance abuse (this is compared with about 30% of people with unipolar depression).

Doctors talk about co-morbidity of substance abuse and mood disorders. "If you see symptoms of substance abuse, you really ought to be looking for symptoms of anxiety and mood too. If you see signs of any one of those three, you should be looking for the other two, because they tend to aggregate together."

Not only do they tend to aggregate, they make the disorder more severe, and the treatment more complex.

These co-morbidities are so common that they often result in misdiagnosis. "People are presenting, and they have panic first, or they have bulimia first, or they have substance abuse first...and they get treated in primary care where they haven't been asked about mood elevation."

Another common misdiagnosis is ADHD in children of bipolar people. Studies show that clinicians should be suspicious of ADHD-like symptoms in the offspring of parents with bipolar disorder - treating these symptoms with stimulants can exacerbate the onset of bipolar disorder in these children.

This can hypothetically feed in to a future comorbidity with substance abuse, according to Dr. Ketter. Children with a first-degree relative with bipolar disorder often present with symptoms of conduct disorder, disruptive behavioral disorder, or ADHD. Then as puberty hits, depression can set in, and many teens will start experimenting with substances to alleviate their moods. "It's almost like the early onset [of symptoms in children with first-degree bipolar relatives] drives the substance abuse comorbidity. And then in later teens, you start getting some mood cycling."

"My sense is that, for manic-depressive illness, pre-pubertal disruptive behavioral disorders, post-puberty depression, substance abuse, and then later on mood-cycling, is one potential pathway that can occur. If we could diagnose earlier and intervene appropriately, things could get better."

Some individuals have a substance abuse history before the onset of bipolar disorder. This demonstrates a hypothetical concept known as kindling - use of substances such as cocaine or alcohol kindles (induces) permanent neurological changes in the brain (particularly in genetically vulnerable people). In these people, the theory goes, the chronic substance abuse kindles the onset of bipolar disorder. Without the substance use, the disorder would not manifest.
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Q: What are the facts about the long-term toxicity potential for lithium?

A: Lithium was FDA-approved in 1970, so we have 35 years of data to look at. Any concerns about long-term toxicity (and there are some that have been raised) have to be balanced by concerns about the consequences of untreated or poorly-managed bipolar disorder.

"If someone's been on lithium for 35 years, what I'm concerned about is their ability to tolerate it might fade a little with age...the ability of the kidney to handle it might fade a little. In those individuals, you may want to use it [lithium] in combination with something else, and maybe taper it a little bit," said Dr. Ketter.

In America, the kind of lithium levels that are "fashionable" are about 0.8 and above (these are blood-level measures of lithium). According to Dr. Ketter, "not everyone needs 0.8" - sometimes lower levels can get the job done. At lower doses, the dangers of long-term toxicity decrease.

"We need to look at how much of the medicine is needed, and what the side-effect burden is."

Considerations for lithium at high doses also include cognitive side effects, and the possibility of emotional blunting.

"If you are having concentration problems - sedation, tremor, these kinds of things - it may be feasible to rearrange the dose during the may be feasible to try a dose that's marginally lower. This is the kind of thing that you really have to negotiate with your psychiatrist. Any changes that you do make should be very gradual."
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Q: How can you tell if someone with bipolar disorder is a good candidate for antidepressants?

A: Use of antidepressants in bipolar is very contraversial. People who have a large depressive burden (for example, people with bipolar II) would seem to be good candidates, but you don't want to give antidepressants to people who can't tolerate them (that is, they cause switching into manias or hypomanias).

According to Dr. Ketter, about 15% of people with bipolar disorder can tolerate an antidepressant plus a mood stabilizer, and will continue to show the improved effects 3-4 months later. Data is showing that for people who continue to look absolutely stable up to 3 months after antidepressant treatment, it may be beneficial to consider continuing the same treatment regimen.

If you are going to go off an antidepressant, you want to taper it off slowly. If the symptoms return within 6 months, there is no guarantee that the same person will respond the same way twice. An antidepressant that made one person manic in the past may not elicite any response the next time around.

Dr. Ketter summed up his opinion as follows: "I think that the data are good enough to support leaving a patient who has done exceedingly well on an antidepressant and mood stabilizer, on the antidepressant treatment. That being said, you can't count on an antidepressant working in the first place."
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Q: When would you consider ECT for a severely depressed, treatment-refractory bipolar patient?

A: "One of the dangers of going to a 'bipolar expert', is that they are so enamored of the new drugs, and the 'Julia Child' (polypharmacy) school of pharmacology, they may not recognize when it's time to move away from medicines and try a completely different way of coming at it" According to Dr. Ketter, both psychotherapy and ECT are important ways to come at bipolar disorder.

One of the limitations of using ECT is that while it can be effective for acute depression, it may not be a good choice for maintenance treatment, or prevention of future episodes. Another potential consideration is that someone undergoing ECT cannot count on being able to function while the treatment is going on. For example, memory deficits occur during the period of the treatments, and "on occassion, people get other types of memory deficits for other times [in their lives] too."

One "classic intervention" for a patient who is not responding is to come off anti-depressants, do ECT treatment, and then go on MAO-inhibitors.

"We are all victims of our own training and our own experience" said Dr. Ketter, who freely admitted that he makes "too few referrals" to the Stanford ECT clinic, mostly because his residency at UCSF did not include ECT training.
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Q: Does anything in the scientific literature suggest what might be the most useful type of educational intervention for bipolar patients?

A: Controlled trials of group psychoeducation, cognitive-behavioral therapy, family-focused therapy, and interpersonal social-rhythm therapy showing that these psychological interventions, as a whole, are effective, especially for acute depression and maintenance therapy. Five studies published in the past year show that effective responses for psychotherapy interventions look like the effective responses for medicines.

In Dr. Ketter's clinical experience, people with bipolar disorder who are also involved with psychotherapy interventions are, on average, taking one less medicine than those who aren't. The average person Dr. Ketter sees in his bipolar clinic is taking about four medicines.

"Perhaps the one thing that unites all these effective interventions is that they have an education module", said Dr. Ketter. Education modules are focused on teaching patients specific coping skills, and helping them cope with specific affects (mood symptoms).

"I think these hybrid psychological techniques, with an educational component, are absolutely crucial," says Ketter.
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Q: What are the effects of bipolar medications on nerve cell growth?

A: Data show that SSRIs and lithium may affect neurogenesis (new brain cell growth) and/or nerve cell repairs.

"What we have found is that the nervous system is not nearly as incapable of repair as we thought in the past. There are certain nerve growth factors (also called neurotrophic factors) that can be stimulated by some of these medicines," Dr. Ketter said.
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Q: Does a psychotic episode that lasts for six months automatically confer a diagnosis of schizophrenia?

A: Not necessarily. "If this were a psychotic manic episode that went on for six months, the answer would be no," answered Dr. Ketter. "It is possible for psychotic mania to last for six months," although this is unusual according to the classic waveform of bipolar episodes (3 months of mania, 6 months of depression).

A psychotic manic episode that lasts for six months is a clue that the next episode of depression will be just as severe.

"On the other hand, if there is not much in the way of emotional features to it, it could be schizophrenia."
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Q: What is the likelihood of bipolar disorder onset after age 60?

A: About 5% of all bipolar onset is in older adults (over the age of 60). In general, the course of an older-onset (as well as an early-onset) bipolar illness tends to be more severe. Older-onset is related to poorer outcome, and the risk of relapse is greater.

Treatment options may be different for this demographic. Sometimes dosages of medications are lower, and the side effects experienced by older patients can be different from what is expected. It is also important to consider interactions of psychiatric medications with any other medications or supplements that the older patient might be taking.
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Q: What options are there for women with bipolar disorder who want to become pregnant?

A: All the major mood stabilizers have some potential to cause birth defects, especially in the first trimester. Literature shows an especially high risk for depakote - some studies suggested a 10% birth defect rate for this medication.

There is more information on the effects of anti-convulsant medications than for the antipsychotics (Editor's note: see this newsblog article for the most recent findings on atypical antipsychotics taken during pregnancy), and more information on the older antipsychotics than on the newer atypicals.

Dr. Ketter recommended exploring the possibility of a "gradual taper" of medication, at least during the first trimester. It is important to monitor closely during this taper; if symptoms begin to reappear, the woman and her doctor should explore other options.

The post-partum period is one of the riskiest times for women with bipolar disorder. "Untreated, 60% of women with bipolar have an episode post-partum", Dr. Ketter reported. Moreover, in his experience, women say that the post-partum episode is the worst they ever had, both in terms of severity and in terms of treatment-resistance.
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Q: What is the role of insomnia in bipolar disorder?

A: Insomnia is a common symptom of manic episodes for people with bipolar. Data show that not sleeping can make manic episodes worse.

"I see patients discover this on their own, how potentially destructive lack of sleep can be," said Dr. Ketter. He acknowledged that it is one of the more seductive aspects of mania - the added energy and time to produce can be very appealing. "The problem is that you end up paying for it, and paying with interest."

Dr. Ketter suggested the following for dealing with insomnia:

  • behavioral methods: no caffeine after mid-afternoon, no evening exercise, etc
  • keep work items (laptops, etc) out of the bedroom - make the bedroom for sleeping
  • some over-the-counter medications help - tylenol PM, melatonin
  • sleeping pills
  • create a "sedative synergy" with medications - for example, taking all of them at night (if you can handle it).

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Q: What role does stress play in bipolar relapse?

A: Several studies have indicated that life events (i.e. stressful/traumatic/major life changes) trigger bipolar episodes. The "kindling hypothesis", which is contraversial but has some evidence to support it, predicts that episodes become more frequent and more spontaneous as one progresses further into the illness. According to this theory, later episodes need less of a trigger (or no trigger at all) to induce them.

"There is no doubt at all that stress can make things worse," said Dr. Ketter. "No matter how biological this appears, we should not discount the role of stress."
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Q: Is there a possible benefit for sleep deprivation therapy in bipolar depression?

A: About 50% of people with either bipolar or unipolar depression will experience mood elevations after only 1 night of sleep deprivation. Unfortunately, the data show that the effects don't last; most people will relapse back into depression.

Dr. Ketter suggested that there is a better likelihood that sleep deprivation might help someone in a depression if it is tried later rather than earlier in the episode. "If you have started a new therapy, you may be able to accelerate the effectiveness [of that therapy] by trying some sleep deprivation effects."

It may be a way, Dr. Ketter continued, to "pull out a single day of function", but the effects typically do not last. In his clinical experience, although some patients experienced hypomania after sleep deprivation, he has never seen someone become manic after just one night of no sleep. "If it is just tried for one night, it may not be so destructive."

According to Dr. Ketter, it might be reasonable for people with all of the following characteristics to consider sleep deprivation therapy for their depressions (always under the direction and supervision of their doctor):

  • patients who are treatment resistant in their depressive episodes
  • patients who are already on a mood stabilizer
  • patients who have never had psychotic symptoms

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Q: Is rapid-cycling a lifelong diagnosis, or can a rapid-cycler become non-rapid cycling later in life?

A: Rapid cycling is not a lifelong diagnosis; it tends to "cut in and cut out." Rapid-cycling in pediatric bipolar disorder may improve as a child develops and passes adolescence.

This conveys significant hope for children and teens with bipolar disorder - getting through the adolescent period can do a lot to stabilize the severity and course of the illness.
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