Focused research on “real world” samples is needed to determine the best treatments that consider each person’s responses to any drug
Pakistani actress Mahira Khan recently revealed that she suffers from bipolar disorder. Photo: @TheMahiraKhan / Twitter
Imagine that you, or someone you know, is diagnosed with bipolar disorder. One drug is prescribed, but you’ve heard that another drug is better. What are your next steps? Are you looking for evidence? And if so, what kind of evidence would you consider?
About 2% of the adult population suffers from bipolar disorder. It can create high levels of suffering, carry suicide risks, and persist for decades. Management options vary, and if you search for information online, it’s easy to become overwhelmed by the many different opinions and interpretations of the ‘evidence’ obtained from clinical trials.
Some medications can be extremely helpful in stabilizing mood, but they can often have side effects. Some medications may be more helpful for some types of bipolar disorder, but how do you know which “type” you or a loved one has?
Clinical specialists, including psychiatrists, often rely on guidelines drawn up by professional organizations to evaluate evidence of treatments. However, there is minimal agreement between many of the current guidelines. A new approach is needed that emphasizes “real-world” effectiveness and respects the observations of people with bipolar disorder.
Two types of bipolar disorder
Already Hippocrates bipolar disorder was known to the medical community. Originally called “manic-depressive psychosis,” it is now known as bipolar I disorder. It was referred to as bipolar II disorder in the mid-1990s. While this second “sibling” has always existed, it was previously seen more as a personality style and was often referred to as “cyclothymia.”
Both bipolar I and bipolar II are characterized by pronounced mood swings. During the highs, people feel energetic and wired. They talk more, spend more and require less sleep but don’t feel tired. They may experience increased sex drive, feel more creative, or so “bulletproof” that they take more risks. Anxiety seems to melt away.
During the “minimum” times, depression comes like a fog. Sufferers can lie in bed for days, deprived of energy. They cannot get any pleasure out of life. Sad and struggling with impaired cognitive ability, they may be at increased risk of suicide.
The key distinguishing feature between the two bipolar conditions is the presence of psychotic features (delusions and/or hallucinations) in those with bipolar I.
Current treatments
Medications are the main way bipolar disorders are managed.
Melbourne psychiatrist John Cade discovered the efficacy of lithium as a treatment for manic depression in 1949. This seminal research ushered in the era of condition-specific psychopharmacology.
Psychiatry can proudly claim its status as an evidence-based discipline. Professionals refer to research-based guidelines to determine the best medications to help stabilize a bipolar disorder.
Options now include lithium, three antiepileptic drugs, several antipsychotic drugs and antidepressants. Although most guidelines place a high value on lithium for both types of bipolar, we personally favor lithium as the drug of first choice only for bipolar I and the anticonvulsant drug lamotrigine for bipolar II.
But evidence isn’t everything
In 2017, our research team reviewed 11 guidelines published by professional organizations. They were all ‘evidence-based’, but we found minimal agreement between them, thus raising questions about their validity. New guidelines have since been issued, but the trend towards minimum agreement continues.
Assessing a psychiatric evidence base is difficult. In medical trials, the tested treatment is compared with a commonly used treatment and/or a placebo. Results from multiple studies are aggregated to compare their overall impact.
But the way study participants are selected to participate in trials presents a problem. Recruitment is generally limited to those with milder conditions, those with no coexisting ailments, or those on limited medications.
Participants may also sign up to get medications for free, which could affect their motivation and reporting. Finally, observations made by treating physicians commonly differ from those made by patients regarding the benefits and side effects of administered drugs.
Thus, there is a strong argument for the need for “real-world” studies that prioritize the opinions of patients with bipolar disorder, rather than judging medications through clinical trials and external evaluators.
Accounting for side effects
In addition to evaluating the effectiveness of any drug, we must evaluate its side effects. For example, lithium may be the right drug for someone with bipolar disorder and, as noted, is the drug most frequently recommended in clinical guidelines. However, it has multiple side effects.
Our 2021 efficacy study compared lithium and lamotrigine in a small sample of patients with bipolar II. For the 28 patients who completed the study, the benefits were similar for the two drugs. But 50% of participants who received lithium experienced distinctive cognitive impairment, side effects that affected their thinking and reasoning.
This is especially concerning because bipolar disorders are known to be overrepresented in people who are creative and high achievers. We suspect, from clinical observation, that lithium is not the best option for bipolar II, and the first author has long observed that it is more cognitively “toxic” to individuals with a bipolar II condition.
Many of the antipsychotic drugs named in the guidelines also have major side effects, including weight gain and diabetes. People who are stable while taking these drugs with no major side effects shouldn’t be alarmed. But these risks support the push for more personalized treatments based on real-life costs and benefits informed by people’s experiences.
We want to hear from people with bipolar disorder
All of these concerns highlight the need for focused research on “real world” samples to determine the best treatments that consider each person’s responses to any drug. We are conducting such a study now, in collaboration with the Black Dog Institute. If you are interested, you can access the study here.
Gordon Parker, professor of Scientia, UNSW Sydney and Michael Spoelma, PhD candidate, UNSW Sydney
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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