In recent months, Brazilian psychiatrist Flávio Kapczinski has been working on two major projects. In one, he is involved in a collaboration seeking to establish a system to classify the progressive degrees of bipolar disorder. Marked by alternating episodes of depression and mania or hypomania, this mental illness affects 3% of the population. If left untreated, the disorder often worsens to the point that patients find it difficult to deal with simple, day-to-day tasks.
After more than 10 years of discussion, an international task force of experts at the 26th Annual Conference of the International Society for Bipolar Disorders, held in Iceland in 2024, reached a consensus on the progression of the illness, considering the number of episodes, the occurrence of comorbidities, and functional impairment.
“It should help doctors choose the most appropriate treatment for each case,” says Kapczinski, who is vice dean of research at the Federal University of Rio Grande do Sul (UFRGS) and professor emeritus at McMaster University, Canada.
In the second project, Kapczinski is working in partnership with the Oswaldo Cruz Foundation (FIOCRUZ) to lead the first study of the prevalence (frequency of cases) of the most serious mental illnesses in a representative sample of the Brazilian population.
Below are the highlights of an interview that Kapczinski gave to Pesquisa FAPESP via video call at the end of October.
In October, you participated in an international task force in Iceland defining the development stages of bipolar disorder. What consensus was reached?
I proposed the creation of this task force 10 years ago. We are now in the third round of the project. In the first, the group, composed of international authorities on the subject, reached a consensus that bipolar disorder can get progressively worse if left untreated. The disorder was first described more than 100 years ago by German psychiatrist Emil Kraepelin [1856–1926], who noticed at the time that some cases evolved in severity. Some patients suffered recurring cases and were hospitalized repeatedly. Sometimes, they were unable to be independent. But his observations were limited because he dealt with inpatients at his clinic.
Has this perception been forgotten?
About 25 years ago, when I started working with bipolar disorder, this view was no longer held. It was believed that schizophrenia led to major functional loss from adolescence onwards and that bipolar disorder occurred in episodes, with no functional loss. In other words, when the episode was treated or overcome, the patient regressed to the baseline level, with no lasting harm. This began to be questioned after the first case registries [studies that followed the populations of entire countries] were created in the Scandinavian countries. In these studies, the researchers noted that every time a patient with bipolar disorder was hospitalized, the likelihood of them being readmitted in the future increased, as did the chance of them going on to develop functional impairments and more severe episodes in the long term.
How did this data influence the field?
Population data from Denmark supported the theoretical progression model that my colleagues and I proposed in 2010. The model classifies the progression of the illness into four stages. The first, we call the latent phase, when the person does not yet show signs of the disorder but has an increased risk of developing it. This risk may present itself in the form of mood swings or depression during adolescence. It is higher when a person’s immediate relatives have bipolar disorder and is exacerbated by drug use, especially cocaine. In stage 1, the illness emerges with no comorbidities. Patients alternate between depression and mania [a state of high energy, euphoria, or impulsivity] or hypomania [a less intense form of mania]. In stage 2, it is accompanied by another problem, such as panic disorder or alcohol dependence, making treatment more complicated. In stage 3, patients suffer functional impairment, and in stage 4, they are completely unable to independently function.
Was the model accepted by your peers?
Other groups see the illness a little differently. A group led by child psychiatrist Anne Duffy of Queen’s University, Canada, determined that the most important thing is to look at the early stages of life. According to the group, sleep problems, anxiety, and attention deficit problems in childhood represent initial manifestations of the illness in children whose parents or siblings have bipolar disorder. Otherwise, their model is similar to what we proposed for adults. Michael Berk, from Deakin University, Australia, believes that the most important factor is the number of episodes a person has experienced. The earliest stage of his model is propensity, meaning people who are most at risk of developing the disorder but have not experienced any episodes. Stage 1 is marked by signs of depression, anxiety, and sleep disturbance. In stage 2, the first episode of mania or hypomania occurs. After the second episode of mania or hypomania, the illness is classified as recurring. It then later becomes chronic. One difference from our proposal is that our model takes into account the person’s level of functioning—their ability to carry out day-to-day activities.
Did the three proposals exist in parallel?
Yes. At the first task force meeting, we reached a more rudimentary consensus: that there is a less complicated early stage without comorbidities in which the person functions well, and a late stage with comorbidities and functional impairment, which is more difficult to treat. It was insufficient, but we were unable to make any further progress than that. We then created a universal nomenclature. We established definitions for an episode; recurrence; neuroprogression [worsening as episodes recur]; risk factors, etc. But the aim of proposing a single staging model [classification of the stages of disease progression] remained out of reach. Ralph Kupka of Amsterdam University Medical Centers in the Netherlands was recently named head of the task force. He and Afra van der Markt, from the same institution, created an ingenious system that considers the number of episodes, the occurrence of comorbidities, and functional impairment. This model accommodates a wide range of clinical pictures and won over many people in Iceland. It is now being consolidated and put in writing. It should be published in mid-2025, and studies will then be able to evaluate its ability to predict treatment responses.
It is important that people understand that bipolar disorder, if left untreated, is a progressive illness
How can a staging model help better treat the disorder?
It should help doctors choose the most appropriate treatment for each case. For example: a person whose parents or siblings have bipolar disorder and who has had depression is at a high risk of developing bipolar disorder if they are only given treatment to resolve the depression. Doctors will have to take this information into account when choosing the appropriate medication. Some antidepressants can trigger what is called a manic switch [from depression to mania].
After a manic episode, is there no going back?
After the first episode of mania or hypomania, what was depression becomes a different illness. It does not go back to being just depression. Staging information can help us better treat these people in the early stages. It also highlights that if there are any comorbidities, they need to be taken care of first. A person with bipolar disorder and panic disorder or substance abuse, the most common being alcohol use disorder, will respond poorly to treatment if the panic disorder or alcohol abuse is not treated first. When the comorbidities are managed, treatment tends to be more effective. Staging also allows individuals to be separated by the degree of complexity.
Why is this separation important?
To make more efficient use of the resources of the public health system. It is not desirable for a patient diagnosed with bipolar disorder who responds well to treatment to be treated at a high-complexity care center. These cases can be treated at a standard health center with support from a CAPS [psychosocial care center] staffed by specialists. More complex cases should be handled by CAPS, in collaboration with a reputable tertiary-care center, usually a university hospital, where patients can be admitted.
Do you have an idea of how the model will be received?
It will not be easily accepted. We, the proponents, have identified advantages. Those who are against it, however, say that the underlying data is insufficient and could therefore cause confusion. Critics say the staging model could stigmatize people and is not useful because in their clinics, they do not see this progression occurring. The group in favor respond that observations in clinics differ from what is seen among the population of a country. The evidence of our proposal will be seen by following a large number of cases over a long period of time. It is important for us that people understand that bipolar disorder, if left untreated, is a progressive illness, just like other mental disorders. We have to look comprehensively at the damage that the illness, if left untreated, can cause to people’s lives, including so that they know what stage they are at and what they can do to reverse or prevent the progression of the illness. Critics say that making a diagnosis and reporting the stage can create stigma. We believe that the less people talk about the issue and the less information they have, the greater the stigma.
When does the disorder usually manifest?
It most commonly arises between the ages of 18 and 35. It primarily affects young adults. However, if you look more closely, you realize that many people who begin to suffer from the illness at 18, 25, or 30 years of age already experienced sleep or attention problems in childhood and impulsive behavior or misuse of alcohol and drugs in adolescence. Often, they already showed symptoms that allowed for a diagnosis of depression, but not bipolar disorder. These people deal with depression for years until closer examination reveals symptoms of hypomania. Delaying a diagnosis of bipolar disorder is harmful and results in more episodes. And a greater number of episodes has an impact on the brain.
Does it affect the rest of the body as well?
In a way, yes. It can stop people from sleeping well and can lead to poor cardiovascular and metabolic health. These people also have a lot of difficulty sticking to diets and exercise routines. They often become sedentary and have an inadequate diet. Individuals with untreated bipolar disorder die 10 years earlier than people without the illness.
Does the mental disorder lead to a pattern of behavior that affects physiology?
There is a debate about this. Our accumulated scientific knowledge of the field indicates that this illness affects biological rhythms, the stability of a person’s diet, sleep, and self-care, and encourages substance abuse. All of this seems to result in accelerated aging and premature death.
Do the medications available to treat bipolar disorder work well?
Each case requires different treatment. Bipolar disorder is chronic and lifelong, like hypertension. Some of the medications used to treat different stages of bipolar disorder are very effective. But some can cause problems. Some increase appetite, potentially leading to weight gain and metabolic problems.
You said that treatment can be effective. What proportion of cases are resolved?
It is difficult to come up with a number. The illness has a manic phase, which is the most serious but also the easiest to treat. The depression can also be effectively treated with a variety of medications. There is no way to measure the success of treatment for both phases.
Ten percent of people who have a first-degree relative with bipolar disorder also develop the illness
How important is genetics?
Heritability is 80%, the highest of all mental illnesses. Translating heritability into common language, we can say that 10% of people who have a first-degree relative with the disorder will develop the illness. In the general population, the occurrence rate is 3%. Seventy percent of people with a bipolar parent also have the illness. Even so, a significant proportion do not develop the disorder. This shows that genetic influence is not deterministic. It only increases the probability. The most important cause is hereditary. Various genes are associated with an increased risk of developing bipolar disorder, each having a small effect.
Are there other factors that increase the risk?
Childhood trauma, particularly sexual abuse, increases the likelihood of developing the illness. Cocaine use also increases the risk. Marijuana too, but to less of an extent.
When should someone who suspects they have bipolar disorder seek medical help?
When the problem is damaging family relationships or affecting their performance at work. When it leads the individual to give up work, turn to drugs or alcohol to alleviate the suffering, or think about suicide.
What is access to diagnosis and treatment like in Brazil?
Access to good mental health care is difficult in the developed world and even more difficult in emerging nations like ours. According to data from the WHO [World Health Organization], only one of every four people with serious mental illness in developing countries will receive treatment.
What is more challenging: identifying the disease or finding the right treatment?
Actually, it is dealing with the increased energy and creativity. Socially, this increased performance is desirable. Society rewards people with a high capacity for work, leadership, and thinking of creative solutions. In the more difficult phases—the depression—the person suffers and is unproductive. Nobody wants that. It is difficult to convince people suffering from hypomania that these characteristics, which they and society consider to be positive, are symptoms of an illness that needs to be treated. We now know that many great artists with bipolar disorder—painters, for example—were more productive when they were in a stable mood, in a stable relationship, with a stable job.
Is the superproductivity of the mania merely an illusion?
During a true manic episode, there is no productivity. The person becomes detached from reality. Their behavior becomes extreme, they get into arguments and fights, often lose their jobs. But in the phases where a person’s mood is just accelerated—what we call hyperthymic, which is just below hypomania—productivity can be very high. In this stage, people are highly charismatic and communicative. They are quick thinking and great at solving problems. This can be a good thing, but it creates a dilemma because people do not want to lose these qualities. Treatment does not eliminate these characteristics, but it prevents people from falling into the extremes, which are destructive. When they realize this, they are more likely to engage in treatment.
How common is bipolar disorder?
Worldwide, type 1 bipolar disorder [with mania and depression] affects 1% of people. Type 2 [with hypomania and depression] affects 2%. So the global total is estimated at 3%. In Brazil, we do not yet have any national statistics. Most Brazilian data is based on information provided by health services. These figures are underestimates because they do not include populations without access to health services. We are therefore beginning a pioneering study in collaboration with Raquel De Boni’s team from FIOCRUZ to determine the prevalence of mental illnesses in Brazil, including anxiety, unipolar depression, bipolar disorder, schizophrenia, chemical dependency, autism spectrum disorder, and post-traumatic stress disorder. The plan is to begin fieldwork in 2025.
How many people will you survey?
Almost 23,000 people aged between 18 and 75 from across the nation. It will be a probabilistic sample, representative of the population. The study has two parts. In the first, 7,800 adults will answer a questionnaire that will screen them for mental illnesses. Then, 20% of them will be interviewed via video call by a specialist who will make a diagnosis. In the second part, 15,000 students, teachers, and technicians from 50 public universities will be screened. Again, 20% will be given a diagnosis. One year later, everyone who went through the diagnostic process will be invited to repeat it. The aim is to measure the incidence of mental health problems [the number of new cases that arise each year]. For the first time, we will have a probabilistic percentage of the population affected by mental illness.
The story above was published with the title “Between extremes” in issue 347 of january/2025.
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