Residual symptoms of insomnia

Good sleep is linked to emotional well-being, while sleep deprivation, even by as little as 1 to 2 hours per night, is associated with problems with alertness, cognition, pain threshold, emotional distress, and mood as well as recurrent health problems.23 In addition, insomnia has been linked to absenteeism and diminished productivity in the workplace.24

While symptoms of insomnia are present in 10% to 60% of the general population, more than 90% of patients with MDD present with comorbid insomnia.23,25 Evidence suggests that recurrent depression is associated with more pronounced abnormalities of sleep neurophysiology as compared with single or initial depressive episodes. In addition, depression with concurrent insomnia predisposes patients to future episodes of depression and anxiety. One of the challenges in identifying insomnia as a residual symptom is the propensity for patients receiving antidepressants to develop treatment-emergent insomnia.3,25

In the 1999 Nierenberg study of 108 subjects who achieved remission based on the HAM-D17 (score ≤7), 44% reported continued insomnia or hypersomnia.10 In a separate study, health-related quality of life (HRQoL) was assessed in 60 outpatients with both depression and insomnia treated with 1 week of open-label fluoxetine followed by 8 weeks of fluoxetine combined with either eszopiclone (for insomnia) or placebo.26 At baseline, patients scored “moderate difficulty” on the Daily Living and Role Functioning (DLRF) subscale and the Relationship to Self and Others (RSO) subscale of the Basis-32. 

At the end of randomized treatment, patients receiving active treatment experienced significant improvement in HRQoL, depression severity, and sleep as compared with patients receiving placebo. Ultimately, resolution of insomnia in depression is likely important for fully restoring HRQoL.26 Limitations of this study include a modest sample size (60 outpatients), the study was powered to detect significant differences in only the primary endpoint of HRQoL, and the 8-week duration of the randomized period was relatively short.26

Evidence-based guidelines for monitoring treatment response

Monitoring treatment response in MDD is an important step in guiding treatment decisions and ultimately assisting patients in achieving remission. In 2008, evidence-based guidelines for treating depressive disorders with antidepressants were published by the British Association for Psycho-pharmacology. At each patient follow-up, the guidelines recommend that treatment response be assessed along with adherence, side effects, and suicidal risk. The use of simple, standardized rating scales are recommended.27

In 2010, the American Psychiatric Association (APA) practice guidelines for the treatment of MDD recommended carefully monitoring patients’ responses to treatment, with a goal of acute treatment achieving remission and a return to full-functioning quality of life. The APA states that throughout treatment, response should be vigilantly and systematically monitored.6 This includes ensuring that treatment has been administered for a sufficient duration and at a sufficient frequency and dose. Structured measures of depression symptom severity, side effects, treatment adherence, and functional status facilitate identification of patients who have not had a complete response to treatment.6

Utilizing validated measures to gauge response to treatment

One tool that may aid patients and providers in achieving remission is the use of measurement-based care tactics. Consistent use of validated instruments allows for accurate assessment of on-going depressive symptoms, better-informed treatment decisions, and support in achievement of sustained remission.28 In addition, monitoring severity of depressive symptoms may identify patients who are at risk for relapse or who may show functional deterioration.29

The majority of MDD treatment studies have used either the HAM-D or MADRS to define remission. The HAM-D is a simple and efficient multidimensional scale originally introduced in 1960 with 17 items.30 It is the most widely used instrument for measuring treatment outcomes in clinical studies. The HAM-D is designed to measure the severity of depressive symptoms in patients with a primary depressive illness. The questionnaire assesses symptoms such as depressed mood, insomnia, agitation, anxiety, and weight loss.30 While the HAM-D should not be used as a diagnostic tool, it enables clinicians to quantify symptom severity, gauge treatment efficacy, and detect relapse.30-32

The MADRS is a 10-question observer-rated scale introduced in 197930 and is commonly used in clinical trials. The MADRS is administered in a clinical interview format, moving from broad questions to more detailed questions, and assesses symptoms of depression such as sadness, insomnia, suicidal thoughts, and changes in appetite and concentration.33,34 It is designed to show change with treatment.34 The MADRS is well validated in younger populations but has not been sufficiently validated in the geriatric population.33,34

While valid, both the HAM-D and MADRS require significant time to administer. Because of this, clinical practice self-report scales that patients can complete “in the waiting room” are often the preferred option. Several widely used, reliable, and validated scales are available in this regard.

The Patient Health Questionnaire-9 (PHQ-9) is a patient-administered validated tool for measuring depression severity as well as for monitoring depression over time in the primary care setting.35 The PHQ-9 may be used as a standardized instrument to quantify baseline intensity and document progress, including response and remission.35,36

The Quick Inventory of Depressive Symptomatology (QIDS) is a 16-item tool designed to assess the severity of depressive symptoms. The QIDS is available both in clinician (QIDS-C16) and self-rated (QIDS-SR16) versions. Both versions are sensitive to change due to medication, psychotherapy, and somatic treatment.37

Recently, the Remission from Depression Questionnaire has been developed to better help clinicians gauge how completely patients who have responded well to treatment are actually in remission. A novel aspect of this scale is that it considers markers of remission that have transcended the simple resolution of depressive symptoms and that have been identified by patients as being particularly important.38

Some scales are designed to assess specific residual symptoms. For example, the Massachusetts General Hospital Cognitive and Physical Function Questionnaire (MGH-CPFQ) is a validated scale designed to measure cognitive and executive dysfunction in mood and anxiety disorders. It has demonstrated temporal stability as indicated by high test-retest reliability. It is sensitive to treatment change and correlates with measures of sleepiness, fatigue, apathy, and neuropsychological functioning. The MGH-CPFQ comprises 7 questions, each rated on a 6-point scale. It is simple to administer and is suitable for use in routine clinical practice.14,16,39

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