SLEEP DISTURBANCES IN BIPOLAR DISORDER

Abstract

NORSK SAMMENDRAG (Summary in Norwegian) Avhandlingen undersøker og beskriver omfang og form på søvnvansker i Bipolar lidelse. Søvnvansker i Bipolar lidelse er vanlig. Forstyrrelser i søvn oppstår ofte som et tidlig varseltegn på depresjon og oppstemte episoder, er et vanlig symptom i affektive episoder og ett av symptomene som henger i lengst etter sykdomsepisoder. Avhengig av definisjoner og metoder, finner vi i tillegg at mellom 70-100% rapporterer søvnvansker også i stabil fase av sykdommen. Avhandlingen baserer seg på data fra: 1) en systematisk oversiktsartikkel over kliniske studier om søvnvansker i stemningsstabil bipolar lidelse, 2) en nasjonal kohort studie om bipolar lidelse hvor deltakerne har svart på spørsmål om søvn, og 3) en lokal klinisk studie hvor vi har fulgt mennesker med stemningsstabil bipolar lidelse og subjektive søvnvansker. Den systematiske oversiktsartikkelen (artikkel 1) fant at minst 50% av pasienter med bipolar lidelse i stemningsstabil fase rapporterer søvnvansker og at 20% fyller kriteriene til en søvnlidelse. Den nasjonale kohort studien (artikkel 2 og 3) fant at både insomni og hypersomni er vanlig i bipolar lidelse, henholdsvis 40% og 29%. Mens insomni var assosiert med depressiv fase i Bipolar lidelse type 2, var hypersomni sterkest assosiert med depressiv eller stemningsstabil fase i Bipolar lidelse type 1. De som rapporterte hypersomni var yngre, hadde oftere Bipolar type 1 og hadde fått foreskrevet antidepressiva, mens de som rapporterte insomni hadde hatt Bipolar lidelse lengre og hadde oftere fått foreskrevet benzodiazepiner og sovemedisin. Ti prosent av de som rapporterte søvnvansker fylte kriteriene for forsinket søvnfase, og gruppen var yngre, hadde høyere BMI og hadde oftere fått foreskrevet stemningsstabiliserende og antidepressive medikamenter enn gruppene med insomni og hypersomni. Den lokale kliniske studien (artikkel 4) sammenlignet stabilitet i søvn-våkenhets-rytmen hos mennesker med stemningsstabil bipolar lidelse, og fant at gruppen med ustabil søvn/våkenhetsrytme var yngre og hadde mer humørsvingninger enn den stabile gruppen. Ti av 11 pasienter diagnostisert med forsinket søvnfase hadde ustabil søvn/våkenhets-rytme og havnet i den ustabile gruppen. I aktigrafimålinger fant vi at gjennomsnittlig aktivitetsnivå ikke varierte mellom gruppene, men at variabiliteten minutt-til-minutt var større i den ustabile gruppen.

SUMMARY Sleep disturbances in Bipolar Disorder (BD) are common, precedes episodes of depression and mania or hypomania as the most common prodrome, and is often one of the last symptoms to disappear after an affective episode. Between 70-100% report disturbed sleep in euthymic state, depending on population included, definitions and methods used. This thesis examines disturbed sleep in BD in three different ways: one systematic review of clinical studies reporting sleep problems in euthymic BD, one national cohort study with systematical assessments of mood and sleep, and one local clinical study with diagnostic criteria and objective sleep measurements. The literature search identified 11 publications. Broadly conceptualized ‘sleep problems’ were reported in >50% of the BD cases on average, but specifically defined sleep disorders such as Insomnia were reported in about 20% BD cases, showing that sleep disturbances are a major clinical issue in BD even in individuals who are currently euthymic. The national cohort study of 563 participants found that more than 40% of cases met criteria for Insomnia and 29% for Hypersomnia. Insomnia was associated with BD II depression whilst Hypersomnia was associated with BD I depression or euthymia. Hypersomnia cases were more likely to be younger, have BD I and being prescribed antidepressants, while Insomnia cases had longer illness durations and were more likely to be prescribed benzodiazepines and hypnotics. Of the 404 adults with BD who met criteria for sleep problems, about 10% of BD cases with a sleep problem met criteria for a DSP profile. The DSP group was younger and had a higher mean Body Mass Index (BMI) than the other groups. Also, DSP cases were significantly more likely to be prescribed mood stabilizers and antidepressant than Insomnia cases. An exploratory analysis of selected symptom item ratings indicated that DSP was significantly more likely to be associated with impaired energy and activity levels. The local clinical study compared two groups with stable and unstable rest-activity (sleep-wake) cycles. 43 patients wore an actigraph for 6-8 days while reporting daily mood and sleep. Patients with unstable rest-activity cycles were younger and displayed more mood variability. Ten of 11 patients diagnosed with Delayed Sleep Phase disorder were in the unstable group, and the unstable group had later and more variable get-up-times and bedtimes. In actigraphy recordings, the mean activity counts did not differ between groups, but the minute-to-minute variability was elevated and increased relative to the overall variability in the unstable group. Conclusion: Whilst Insomnia symptoms are common in BD, Hypersomnia is a significant and frequently underexplored problem. Detailed analyses of large representative clinical samples are critical to extend our knowledge of differences between subgroups defined by Sleep Profile. The DSP group identified in this study can be differentiated from Hypersomnia and Insomnia groups on the basis of clinical and demographic features. The association of DSP with younger age, higher BMI and impaired energy and activity also suggest that this clinical profile may be a good proxy for underlying circadian dysregulation. A subgroup of euthymic patients with BD displayed unstable rest-activity cycles combined with mood variability and motor activity patterns that resemble findings in affective episodes..