There is a controversial trend in the treatment of bipolar disorder to prescribe antidepressants to patients suffering from the less unstable forms of the disorder. In the past, antidepressants were often prescribed to those patients who experienced long periods of depression with only brief episodes of mania – the most commonly recognized symptom of the disorder – affecting that antidepressants are then prescribed where they aren’t necessarily the best choice (Ghaemi, 2001). Generally, this possible error in judgment has been linked to studies that have shown them to be effective in the treatment of unipolar disorder, as well as because those with bipolar disorder are often excluded from studies on antidepressants because of other medications that they are currently taking (Torrey and Knable, 2002, p. 164). This has led to the assumption that, because it is effective with unipolar disorder, that antidepressants would also be effective in treating the depressive stages of bipolar disorder. There is also the factor that it is commonly misconceived that all bipolar patients are manic, while for the most part they are depressed, leading to unfortunate misdiagnoses since mania is the factor that is mistakenly looked for when diagnosing the disorder (Ghaemi, 2000). Most bipolar patients experience only infrequent and brief bouts of mania, but are mostly depressed (Goodwin and Jamison, 1990). However, it has recently been shown that antidepressants can cause further complications with the disorder, rather than alleviate its symptoms, prompting a call for better care in diagnosis and treatment. The use of antidepressants is strongly cautioned against by most experts.
As well as the caution over the dangers of antidepressants, the amount of data available that proves the effectiveness of antidepressants in treating bipolar disorder is shockingly limited (Torrey and Knable, 2002, p. 163). Antidepressants and their effects on unipolar disorder is a much more deeply researched area than that of the effects on bipolar disorder (Ghaemi, 2001). As mentioned above, this is largely due to the fact that most people suffering from bipolar disorder who are otherwise eligible for inclusion in studies have been prescribed a medication that excludes them from the project. However, the successes with unipolar disorder do not justify the use of antidepressants well enough to allow their use on bipolar disorder. Approximate estimates by Herbert Wagemaker, MD, based on experience and observation, show that for the three different types of antidepressants – tricyclic, monoamine oxidase inhibitors (MAOIs), and Selective Serotonin Reuptake Inhibitors (SSRIs) – there is a risk of rapid cycling, particularly tricyclic antidepressants - which caused cycling in about 25% of patients – and MAOIs, where the risk was about 12% - 21% (p. 70). According to S. Nassir Ghaemi, MD, even within the studies that have been done, “the antidepressants have not yet proven their worth” (2001). Ghaemi also states that studies with the newer antidepressants are “practically nonexistent” and that there is “almost no idea from controlled studies of the long-term effects of antidepressants in bipolar disorder”; Bupropion and paroxetine have shown minor benefits and cause lower rates of acute mania than tricyclic antidepressants, but “no antidepressant has been proven safe or effective in the long-term treatment of bipolar disorder” (2000).
Despite the lack of suitable studies to reveal concrete benefits of antidepressants in treating bipolar disorder, there is a current shift towards caution against their use for the reason that they have shown to have harmful effects on certain forms of the disorder. According to Jim Phelps, M.D, in bipolar I patients - those suffering from manic episodes rather than simply depression - “depressed patients given antidepressants switch into full mania between 30-50% of the time” (2003). In bipolar II, where depression is the factor that is most apparent, SSRIs – the newest type of antidepressants available – are associated with both a lower level of depression in patients as well as a higher risk of manic symptoms (Ryan, 2003, p. 261). Dr. Phelps also suggests evidence that the use of antidepressants can cause a low response rate to later treatments with drugs such as valproate (commercially known as Depakote); those previously treated with antidepressants were found to be less responsive to valproate than those who had never been placed on antidepressants before, suggesting a previously unnoticed permanent change in the patient caused by the medication (2003). Phelps states that “antidepressants may worsen a problem which might have been milder and more treatment responsive had that type of medication never been used”, although the extent of that risk is still debatable (2003). Ghaemi suggests that those bipolar patients who continue their use of antidepressants may lessen the chance of prescribed mood stabilizers from working, as well as causing an increase in future episodes of mania, meaning that the antidepressants work as a form of counterproductive “mood destabilizers” (2000). It is recommended that antidepressants be tapered off after recovery from the depressive stage, but data shows that this is not what is commonly occurring, and that antidepressants are instead used for long-term treatment (Ghaemi, 2000).
Alternatives to antidepressants are available, although they are not used as often as antidepressants, which statistics have shown are the most commonly prescribed drugs for bipolar disorder, particularly in the United States (Ghaemi, 2001). The second most common prescription, when the disorder is effectively diagnosed, is lithium, which is one of several successfully used mood stabilizers. Initially used as a treatment for epileptic seizures (as with many of the approved mood stabilizers), it is not known exactly how lithium works in regards to treating bipolar disorder, although it has been shown to affect the communication between nerve cells, aiding recovery from effects of bipolar disorder (Phelps, 2004). Several studies have been done to discover whether lithium is effective in long-term treatment – studies that have ranged up to three years – and it is currently recognized as a useful drug in treating bipolar disorder. Unfortunately, a relatively high dose of lithium is required if it is used by itself – about 900 mg – but the medication can, and usually is, prescribed in combination with a second mood stabilizer so that the doses of both drugs can be kept low, preventing any of the possible side effects (Phelps, 2004). High doses of lithium can be dangerous, but because of the combination method of prescription and close monitoring of levels of the drug in the blood, dangerous reactions can usually avoided. Research on how Lithium truly reacts with the body is very actively being pursued.
Unlike antidepressants, lithium actually has a record of exhibiting no side-effects whatsoever within the proper dosage range. There are mild reactions, such as a dry mouth, nausea, or mild tremors, but nothing life-threatening and nothing that causes the symptoms of bipolar disorder to worsen. It is only if the patient becomes severely dehydrated or through a reaction to another medication such as ibuprofen that a complication may arise. There are also other mood stabilizers that can aide in the treatment of bipolar disorder, although they are less commonly prescribed for various reasons (Phelps, 2004).
For example, valproate is a another commonly prescribed mood stabilizer that has proven effective, exhibits no side effects, and is usually the second choice next to lithium. In the case of valproate, the side-effects are even less than those of lithium, as it causes only mild effects such as nausea upon first starting treatment and nothing else when kept at a relatively low dosage (Phelps, 2004). It has been shown to react very quickly, as compared to lithium, and studies show that it is best for treating those who have a history of rapid cycling, making it a good alternative when lithium fails to work (Torrey and Knable, 2002, p. 149). This may explain why it is prescribed after antidepressant use has been discontinued, as evidenced by the aforementioned study in which it was discovered that a history of antidepressant use lessened the effectiveness of valproate. Unfortunately, valproate has been shown to be ineffective at treating the depression associated with bipolar disorder, making it a second choice in favour of lithium (Torrey and Knable, 2002, p. 149). Again, however, it is a good choice for a combination prescription, making it possible to get the benefits of both lithium and valproate.
Other medications, such as carbamazepine, also have shown to be effective in treatment, although certain side-effects have given rise to a need for caution. When compared to a placebo, lithium, and an antipsychotic drug, carbamazepine was shown to be as effective as lithium in the treatment of mania (Torrey and Knable, 2002, p. 152). However, it is known to cause several undesirable side effects, the worst of which is a rash caused by an allergic reaction, which occurs commonly, and the possibility of the development of Stevens-Johnson Syndrome, a fatal skin condition, although this is a rare occurrence (Phelps, 2004). As well, there is the chance of effects such as sleepiness, confusion, and abnormal heart rhythms (Torrey and Knable, 2002, p. 153- 154).
Even what few studies have actually been done on the effects of antidepressants fail to show a significant excuse for their wide-spread use. Clinicians Ross Baldessarini and S. Nassir Ghaemi, as described in Ghaemi’s 2001 article, reportedly discovered a mere six studies on the effects of antidepressants on patients with bipolar disorder, one of which was actually only a study using bipolar type II patients and did not properly measure manic symptoms. From the rest, those using a Lithium control arm failed to show any evidence that the antidepressants could even match the effectiveness of mood stabilizers, let alone that they were a better choice. The antidepressants were not proven to be effective on their own, but only when used in conjunction with mood stabilizers. Combinations of mood stabilizers without antidepressants have also been shown to be as effective (Ghaemi, 2001).
Unfortunately, these studies show only that antidepressants fall short of mood stabilizers in their effectiveness, not that the antidepressants themselves are a danger. There have not been enough proper studies and therefore there is not enough evidence to disprove their use entirely. A National Institute of Mental Health sponsored study has, for example, shown that other factors, and not simply antidepressant use, can cause rapid cycling in bipolar patients, leading to further obscurity on the matter (Ghaemi, 2001). Studies based simply on bipolar disorder have shown results that leave the matter inconclusive as to whether it is indeed antidepressants that cause rapid cycling. As well, there is undeniable evidence that an abrupt shift off of antidepressants carries the risk of sending the patient into a severe depression.
Still, it is enough to raise the question of why antidepressants are still the primary choice to be prescribed, since mood stabilizers have consistently tested as having better results. There are many complications that arise from the issue, but one thing is generally clear: the use of antidepressants for long-term treatment of the symptoms of bipolar disorder carries significant risk, if not actual danger. Mood stabilizers are a far more reliable choice, regardless, although for the sake of clarity more studies need to be done.
Sources Cited
Gaemi, N. (2000, October). Antidepressants in Bipolar Disorder: Are They Safe? Are They Effective? Bipolar Insights. Retrieved February 3, 2004 from http://www.mhsource.com/bipolar/insight1000.html
Ghaemi, N. (2001). Bipolar and Antidepressants: An Ongoing Controversy. Primary Psychiatry, 28 - 34 Retrieved February 3, 2004 from http://www.cmeondemand.net/PP/ConsiderThis/ PP201_Ghaemi.html
Goodwin FK, Jamison KR (1990), Manic-Depressive Illness. New York: Oxford University Press.
Phelps, J. (2004). Retrieved February 2, 2004 from http://www.psycheducation.org
Ryan, N. (2003). The Pharmacological Treatment of Child and Adolescent Bipolar Disorder. In Geller, B., and DelBello, M. (Ed.) Bipolar Disorder in Childhood and Early Adolescence (p. 255 – 271) . The Guilford Press.
Torrey, F., & Knable, M. (2002), Surviving Manic Depression. New York: Basic Books.
Wagemaker, H. Schizophrenia and Bipolar Disorders: Often Misdiagnosed Often Mistreated: A Family Manual. Ponte Vedra Publishing.