Five New Insomnia Subtypes May Help Personalize Treatment

Dutch researchers have identified five novel subtypes of insomnia, which may lead to more personalized treatments for insomnia.

The subtypes are largely unrelated to sleep complaints but rather are differentiated by biologically based traits and life history. They are stable over time and are associated with comorbid depression, treatment responses, and findings in encephalographic event–related potentials, the investigators note.

The study was published online January 7 in Lancet Psychiatry.

Data-Driven, Bottom-up Approach

Previously proposed subtypes of insomnia disorder were developed "top-down" and focused on sleep-related characteristics, such as difficulty falling asleep or staying asleep. However, they were insufficiently reliable and were largely discarded, Tessa Blanken, a doctoral candidate in the Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Amsterdam, and colleagues point out.

They suspected that "clearer subtypes of insomnia disorder might emerge if they were developed bottom-up and data-driven with a multidimensional set of stable, biologically based non-sleep characteristics that are relevant to insomnia."

To investigate, the researchers analyzed data on 4322 adults from the Netherlands Sleep Registry who completed questionnaires on personality traits, sleep, life events, and health history.

Of these, 2224 (51%) had probable insomnia disorder, defined as having an Insomnia Severity Index (ISI) score of at least 10. The remaining 2098 (49%) had lower ISI scores and served as control participants.

Using latent class analysis of the questionnaire responses of the insomnia group, the researchers identified the following insomnia disorder subtypes:

Subtype 1 (19% of the group), characterized by high scores on many traits of distress, such as neuroticism and feeling down or tense. This subtype is termed "highly distressed insomnia disorder."

Subtype 2 (31%) and subtype 3 (15%), characterized by less distress. These subtypes are distinguished on the basis of the patient's being either sensitive or insensitive to reward. Subtype 2 is termed "moderately distressed, reward-sensitive insomnia disorder," and subtype 3 is termed "moderately distressed, reward-insensitive insomnia disorder."

Subtype 4 (20%) and subtype 5 (15%) are characterized by less distress. They differ in the degree to which patients experience insomnia in response to stressful life events.

For patients with subtype 4, stressful events induce severe and long-lasting insomnia, whereas for patients with subtype 5, sleep is unaffected by such events.

Subtype 4 is termed "slightly distressed, high reactive insomnia disorder," and subtype 5, "slightly distressed, low reactive insomnia disorder."

These subtypes emerged as specific, multivariate profiles of stable characteristics that were not directly related to sleep but were relevant to insomnia, the researchers note.

In a subsample of 215 of the original 2224 patients with insomnia who were reassessed 4.8 years later, the probability of the patients' maintaining their original subtype was 0.87, "indicating a high stability of the classification," they write.

They replicated the insomnia subtypes in a second, nonoverlapping dataset from the Netherlands Sleep Registry of 251 adults with insomnia disorder. The characteristics of these insomnia disorder subtypes differed from those of control persons who did not have insomnia disorder.

Ready for Prime Time?

The researchers indicate that it is feasible to conduct subtyping using a concise set of questions that they have made available in the appendix of the article and that includes automated scoring.

However, Blanken cautioned that more studies are needed before healthcare providers can directly use these subtypes to individualize treatment.

She said she and her colleagues are currently conducting a large clinical trial to investigate whether the different subtypes can be used to identify people who suffer from insomnia and who are at highest risk for depression. They are also exploring "whether giving these individuals CBT-I [cognitive-behavioral therapy for insomnia] complemented by chronotherapy (or not — these are different experimental conditions) can help to prevent the development of depression. This study is still ongoing."

In an accompanying commentary, Tsuyoshi Kitajima, MD, PhD, from the Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan, writes that this research suggests that "robust subtyping is possible among a population with insomnia. This new subtyping approach might add a new page to the history of the insomnia nosology, promoting discoveries of new mechanisms and different interventions.

"Further replications of these subtypes among populations with insomnia disorder within clinical settings would be valuable," Kitajima notes.

Funding for the study was provided by the European Research Council and the Netherlands Organization for Scientific Research. The authors have disclosed no relevant financial relationships. Dr Kitajima has received research grants from Eisai, Takeda, and Merck Sharp & Dohme and personal fees from Eisai, Takeda, Merck, Mitsubishi Tanabe Pharma, Otsuka, Eli Lilly, Meiji, Yoshitomiyakuhin, Sumitomo Dainippon Pharma, Fukuda, Shionogi, and Novo Nordisk.

Lancet Psychiatry. Published online January 7, 2019. Abstract, Comment

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