Co‐occurring depression and insomnia in Australian primary care: recent scientific evidence

The frequent co‐occurrence of depression and insomnia has been recognised for many years.1 Up to 90% of patients with mood disorders also report difficulties initiating and/or maintaining sleep, and about 20–50% of patients with insomnia disorder report symptoms of depression.2,3 Indeed, the overlap of impaired sleep and depressed mood is reflected in diagnostic schemas for both disorders. Diagnostic criteria for major depressive disorder (Box 1) include insomnia or hypersomnia among central symptoms,4 whereas criteria for insomnia disorder may include mood disturbance among the required daytime sequelae.4 The co‐occurrence of depression and insomnia is associated with reduced quality of life, greater overall morbidity, and increased health care use, compared with either depression or insomnia alone.2,5 Therefore, it is critical to consider diagnostic and management approaches for patients with co‐occurring depression and insomnia to improve patient outcomes and reduce health care costs. This narrative review presents recent scientific evidence regarding the diagnosis and management of co‐occurring depression and insomnia, to challenge outdated conceptualisations of “secondary insomnia” and present Australian primary care practitioners with a conceptual model to manage patients with both disorders.

Implications of secondary insomnia

When depression and insomnia co‐occur, the depression is commonly conceptualised as the primary disorder, and the insomnia as a secondary symptom.2,3,6,7 This is evidenced by clinicians prioritising the management of depression over insomnia, and an expectation that insomnia symptoms will abate when depression is successfully managed.6,8,9 For example, a 2020 Productivity Commission inquiry report on mental health omitted the impact of insomnia on mental health,10 and outlined referral models in primary care that are tailored to the management of depression, anxiety, stress and psychosis over insomnia (eg, mental health treatment plans). In the context of depression, conceptualisations of secondary insomnia imply that the insomnia symptoms are directly dependent on the depression and that sleep will not improve until treatment for depression is initiated and depression remission is achieved.11,12

Although it is likely that depression initially contributes to sleeping difficulties in many individuals, insomnia symptoms can rapidly develop functional independence from the initial triggers (eg, depression) and bi‐directional relationships between insomnia and initial triggers can form, whereby mechanisms and manifestations of each disorder may exacerbate the other.1,2 Therefore, when insomnia symptoms persist for at least 3 months (ie, chronic insomnia),4 targeted management of the insomnia is recommended.

Recommended treatments for depression and insomnia

The most common approaches to treat depression include non‐pharmacological strategies (eg, cognitive behaviour approaches including behavioural activation) and pharmacological management (eg, antidepressants).13,14 See Box 2 for an overview of strategies to treat depression.

The most effective treatment for insomnia is non‐pharmacological cognitive behaviour therapy for insomnia (CBTi; Box 2).22,26 Indeed, the Royal Australian College of General Practitioners guidelines on benzodiazepine prescribing and insomnia management recommend that CBTi strategies should be used as the first line treatment for insomnia.22 CBTi commonly includes 6–8 weekly sessions, delivered by trained health care professionals (eg, psychologists), or self‐administered through reading materials or interactive online programs. General practitioners may also administer CBTi over the course of four to five weekly or fortnightly appointments.23 CBTi includes a range of educational, cognitive and behavioural strategies which aim to identify and treat the underlying psychological, behavioural and physiological factors that maintain the insomnia disorder.23 For this reason, CBTi leads to clinically significant sleep improvements which are sustained long after the cessation of therapy. Online CBTi programs have received a large amount of research attention in the past decade and may be a particularly useful to support access to CBTi during the current coronavirus disease 2019 pandemic and in rural and remote communities.

Although sedative‐hypnotics (eg, benzodiazepines, z‐drugs [eg, zopiclone, eszopiclone, zolpidem]) represent the most common management approach for insomnia in Australian primary care patients,27 these medicines are not recommended as first line treatment, or for the long term management of insomnia.22,28 Sedative‐hypnotics are associated with negative side effects, adverse events and risk of pharmacological tolerance, dependence and misuse.29 It is recommended that sedative‐hypnotic management of insomnia be restricted to patients who are not suitable for or do not respond to CBTi, and that these medicines should be prescribed at the lowest effective dose for the shortest possible duration.22 Although melatonin (an endogenous hormone associated with circadian rhythm control) is not associated with the same dependence risk or side effects as benzodiazepines and z‐drugs, melatonin is not recommended as first line treatment for insomnia, or as a long term management approach (> 3 weeks), due to limited evidence.22 Melatonin has primarily been used to manage circadian rhythm disruption and disorders (eg, jet lag, delayed sleep–wake phase disorder) rather than insomnia (which is maintained by separate psychological and behavioural factors). Over‐the‐counter medicines for insomnia (eg, antihistamines, herbal and nutritional substances) are not recommended for the management of insomnia, owing to limited efficacy data.22

Finally, there is a growing trend for off‐label antidepressant and antipsychotic prescriptions to manage insomnia.8,27 In the context of severe depression with comorbid sleeping difficulties, or when a patient history clearly indicates that the depression is the chief complaint and preceded the insomnia, clinicians may initially trial an antidepressant, which may acutely improve sleep, enhance daytime energy levels and activity, and reduce depression. The clinician may then target any residual insomnia symptoms with either a short term sedative‐hypnotic30 or CBTi.31 Indeed, a 2019 Cochrane review found that combined antidepressant plus benzodiazepine therapy was more effective than antidepressants alone in improving depression severity in the first 4 weeks of treatment. However, the beneficial effects were not maintained, and those using combined therapy were more likely to report at least one adverse effect.30 The evidence does not currently support long term use of combination therapy.

The increased use of antidepressants to manage insomnia8,27 may also be due to a combination of conceptualisations that insomnia is a secondary symptom of depression, and guidelines recommending against sedative‐hypnotic prescriptions, which collectively encourage practitioners to prescribe antidepressants and antipsychotics.22 However, there is very limited controlled trial evidence to support this approach.28 A 2018 Cochrane review of the effect of antidepressants on insomnia assessed 23 randomised controlled trials (RCTs), and reported low quality evidence for short term effects of low dose doxepin and trazadone on insomnia.32 The authors concluded that these were “mostly small studies with short‐term follow‐up and design limitations”.32 A meta‐analysis of nine RCTs investigating the effect of tricyclic antidepressants on objective (polysomnographic) sleep of insomnia patients reported improved sleep parameters but an increased risk of side effects and study attrition compared with placebo.33 Antidepressants and antipsychotics are therefore not recommended as first line or long term treatment for insomnia (or insomnia comorbid with depression or mood disorders).22,34

Insomnia and depression may also co‐occur with other sleep disorders including obstructive sleep apnoea35 and circadian rhythm disorders (ie, advanced or delayed sleep–wake phase disorder).28 It is important to distinguish insomnia from these other sleep disorders (which also commonly co‐occur with depression), as different management approaches are recommended.28

Insomnia requires targeted diagnostic and treatment attention

In the six sections below, we review scientific evidence regarding the management of co‐occurring depression and insomnia. This evidence suggests that primary care practitioners should consider non‐pharmacological CBTi strategies to not only improve sleep but also to improve pre‐existing depression symptoms, enhance the effect of adjunct depression treatment, and potentially reduce the likelihood of future (incident) depression (Box 3). This approach represents a shift from dated conceptualisations of secondary insomnia toward conceptualisations of insomnia as a comorbid condition which is responsive to targeted treatment, managed in a holistic patient‐centred model of care (ie, targeted treatments for both conditions). The Royal Australian and New Zealand College of Psychiatrists and other medical and primary care organisations recommend that clinicians should consider sleep problems as an important treatment target when co‐occurring with other conditions including depression.12,22,36

Insomnia is commonly an independent disorder

Chronic insomnia (persisting for ≥ 3 months) is commonly maintained by underlying psychological, physiological and behavioural factors that operate independently of comorbid conditions.4,22 Although sleeping difficulties may initially occur alongside predisposing factors (eg, tendency to internalise, negative ruminations) and temporal and contextual triggers (eg, work–life stress, acute depression, jet lag), insomnia can rapidly become a self‐perpetuating and chronic condition even after these initial factors are resolved.37 Common underlying factors of insomnia include sleep‐related cognitions or beliefs that increase anxiety/arousal about sleep (eg, catastrophising over the consequences of sleep loss, and misconceptions about “normal sleep”), and maladaptive behaviours, such as spending more time in bed than is necessary (leading to a conditioned arousal response to the bedroom environment), excessive caffeine consumption to alleviate daytime fatigue, napping for too long in the late afternoon and reducing subsequent sleep “pressure” in the evening, and inconsistent sleep–wake schedules that are misaligned with the internal body clock.38 These underlying factors can cause physiological and psychological changes that result in perceived sleep loss and daytime impairments (eg, a state of chronic 24‐hour hyperarousal triggered in the bedroom environment while attempting to sleep), which perpetuate the insomnia cycle.39

After chronic insomnia has developed, alleviation of the initial triggers (eg, depression) will have little impact on improving the insomnia condition. Therefore, targeted treatment of insomnia with CBTi is the recommended treatment for patients with chronic insomnia, including chronic insomnia co‐occurring with other conditions.22,26

Insomnia symptoms predict future depression

Multiple longitudinal cohort studies have reported that insomnia symptoms predict increased risk of future depression.40,41,42 For example, a meta‐analysis of 21 studies found that insomnia symptoms predicted future depression 1–34 years later (odds ratio [OR], 2.60; 95% CI, 1.98–3.42).43 Alternatively, a meta‐analysis of ten studies reported that insomnia was also significantly associated with the onset of future depression (OR, 2.83; 95% CI, 1.55–5.17), anxiety, alcohol misuse and psychosis.40 An Australian longitudinal study reported that among 5702 young women, those with frequent sleep disturbance at baseline had a greater risk of depression (OR, 4.4; 95% CI, 2.8–7.0) and anxiety diagnosis (OR, 2.9; 95% CI, 1.6–5.2) 9 years later.44

This temporal relationship suggests that insomnia commonly precedes depression, and therefore highlights the possibility of early identification and treatment of insomnia to prevent depression onset.43 There are several potential mechanisms by which insomnia may increase risk of depression, including modified emotional regulation and reactivity,38,43 behavioural inactivity resulting from perceived sleep loss and daytime impairments,38 patterns of negatively toned and ruminative cognitions experienced during prolonged nocturnal awakenings,42 and side effects of sedative‐hypnotics commonly prescribed to manage insomnia.29,45,46

In contrast, a smaller number of studies assessing the predictive role of depression on future insomnia have reported mixed results.42,47,48 These temporal associations highlight a clear flaw in conceptualisations of secondary insomnia in patients with co‐occurring depression and insomnia.

Treating insomnia can prevent onset of first time depression

Given the temporal association between insomnia and incident depression, and the effect of CBTi on improving depression symptoms,49 recent RCTs have sought to investigate whether CBTi reduces rates of new‐onset depression.50,51 A 12‐month RCT investigated the effect of digital CBTi versus online sleep education control on prevention of depression in 1358 individuals with insomnia.51 A total of 658 patients with insomnia completed the 1‐year follow‐up (including 358 in the treatment and 300 in the control group). Among individuals without depression before treatment, the 1‐year incidence of depression was significantly lower in the CBTi (9.6%) than the control group (18.8%). These data suggest that early identification and treatment of insomnia can prevent the future onset of depression.

An Australian trial also investigated the effect of online CBTi on reducing depression symptoms among participants with insomnia and depression symptoms.50 Although CBTi improved depression symptoms compared with the control group, there was no between‐group difference in major depressive disorder diagnosis at 6‐month follow‐up. The authors noted that this may have been due to inadequate power, as a small number of participants developed major depressive disorder during the study (n = 22; 2%).50

Treating insomnia improves depressive symptoms

Several meta‐analyses have reported that CBTi improves depression symptoms.31,52,53 For example, an examination of ten studies investigating the effect of CBTi on depression outcomes in patients with co‐occurring depression and insomnia reported that CBTi may represent a suitable stand‐alone treatment for co‐occurring depression and insomnia, or combination treatment alongside antidepressants.31 Another meta‐analysis of ten RCTs of online CBTi programs reported a significant effect on reduced depression.52

A 2017 RCT directly compared the effects of 9 weeks of online CBTi with 9 weeks of CBT for depression in 43 patients with co‐occurring depression and insomnia.45 CBT for depression included educational components, two sessions of behavioural activation (increasing positively reinforced activities, and handling negatively reinforced activities), registration and reappraisal of negative thoughts, anxiety and worry, and prevention of relapse. The CBTi intervention also included educational, behavioural and cognitive components, as well as education about sleep medicines, stress and fatigue management, and relapse prevention. Patients in the CBTi group experienced significant improvements in symptoms of both depression and insomnia. However, patients in the depression treatment group experienced improvements in depression only. Surprisingly, there was no significant difference in reduction in depression between the group receiving CBT for depression and the group receiving CBTi. The authors suggested that insomnia symptoms may require specific CBTi components to improve, while depression may require non‐specific, albeit high quality treatment. It was also proposed that insomnia symptoms may have preceded and directly contributed to the maintenance of depression in these participants, which therefore resulted in improved depression severity as the insomnia was treated with CBTi.45

There is limited scientific evidence demonstrating that depression treatment improves insomnia. Although anecdotal reports, short term studies, RCTs with short follow‐up, and case reports indicate that some antidepressants may improve sleep in select patients,32,54 there are limited long term controlled trial data demonstrating the effectiveness or safety of this treatment approach.28,32

Insomnia symptoms may reduce response to depression treatment and increase depression relapse

Insomnia symptoms often persist after depression treatment,45,55 and may impair the effect of depression treatment on reducing depression severity and relapse.7,56 As insomnia increases risk of future depression, it is possible that residual insomnia symptoms persisting after depression treatment may contribute to increased depression relapse. Indeed, a study found that after management of depression with combined psychotherapy and pharmacotherapy, patients with residual insomnia symptoms were more likely to experience recurrence of depression during follow‐up (65% recurrence) compared with those without insomnia (13% recurrence).56 In addition, a study used data from Project IMPACT7 to examine the relationship between persistent insomnia symptoms and response to depression treatment administered in primary care clinics. Patients with persistent insomnia were found to be 3.5 times more likely to remain depressed at 12‐month follow‐up compared with patients without insomnia (continued depression defined by < 50% improvement by 12‐month follow‐up).7 Neglecting to manage co‐occurring insomnia may therefore undermine the benefits of depression treatment over time.

Depressive symptoms may impair response to insomnia treatment

Several studies have also investigated whether depression symptoms impair the effectiveness of CBTi. Although some studies have reported that patients with depression and/or psychiatric symptoms experience less improvement of insomnia following CBTi,57,58 most studies have reported no association between depression symptoms and reduced response to CBTi. 59,60 For example, a recent study investigated the effect of symptoms of depression, anxiety and stress on response to CBTi in 455 patients with chronic insomnia attending a hospital outpatient CBTi program.49 Although patients with co‐occurring severe depression symptoms reported greater severity of insomnia before treatment compared with insomnia patients with low depression symptoms, there were no differences in changes in insomnia symptoms during CBTi between groups (Box 4).49

It is possible that some patients with co‐occurring depression and insomnia continue to experience daytime impairments (ie, shared symptoms including daytime fatigue, lethargy and poor mood) following CBTi, thereby decreasing the measured improvement in overall insomnia symptoms in some studies (when insomnia severity is measured as both nocturnal and daytime symptoms; Box 1). More research is required in this area to understand the mechanisms by which depression may undermine the effectiveness of CBTi in improving insomnia (ie, whether the insomnia is in fact secondary among some patients, or whether the depression indirectly reduces improvement of insomnia through reduced engagement or adherence to therapy).

Treatment recommendations

There are several potential options to access CBTi in primary care. Box 2 provides referral and management options for both depression and insomnia, while Box 3 presents an overview of a conceptual management approach for co‐occurring depression and insomnia in primary care. Given the common comorbidity of insomnia and depression, we recommend that patients who present with symptoms of either disorder are routinely assessed for the other (eg, a patient presenting with depression symptoms should be assessed for comorbid insomnia, and vice versa). Brief validated screening tools for insomnia18 and depression16 may be used, in addition to other measures and questions to assess for additional comorbid conditions and sleep disorders.35

If a patient reports both depression and insomnia, consider targeted treatments for both disorders. Choice of (i) initial depression treatment (eg, psychotherapy, antidepressant), (ii) concurrent depression and insomnia treatment, and (iii) initial insomnia treatment (eg, online, face‐to‐face CBTi) should be based on a patient’s preference, the severity of each condition, patient history, previous management of the insomnia and depression, other comorbidities (including comorbid sleep disorders) and lifestyle factors. Assessment of a patient’s history may include information about the temporal onset of the depression and insomnia (ie, which disorder occurred first). Although this may be helpful in determining the main reason for seeking treatment, targeted treatment for both conditions should be made available when they co‐occur. Even when insomnia symptoms occur after depression onset, the insomnia can quickly develop functional independence of other symptoms/disorders and become maintained by independent cognitive, physiological and behavioural factors.37,38

Where depression is considered the primary condition chronologically (patient history) or the patient presents with moderate‐to‐severe depression (severity), CBT for depression could be considered first, followed by or concurrent with an antidepressant, particularly if the depression is severe. CBTi should also be made available, particularly if the comorbid insomnia appears to be maintained by insomnia‐specific perpetuating factors (eg, excessive sleep‐related focus, daytime napping, and extended time spent in bed), if the insomnia does not resolve, or if the insomnia appears to undermine the effectiveness of targeted depression treatment. Importantly, based on the research reviewed above, we recommend that treatments for both conditions should be made available to all patients with co‐occurring depression and insomnia symptoms.

Conclusion

Depression and insomnia commonly co‐occur and result in increased morbidity for patients and complex diagnostic and treatment decisions for clinicians. Although it is common for primary care practitioners to conceptualise insomnia as a secondary symptom of depression, this belief is not supported by scientific evidence. Instead, evidence suggests that depression and insomnia represent two comorbid disorders, which are potentially maintained by both bi‐directional and functionally independent mechanisms. It is recommended that when managing patients with co‐occurring depression and insomnia symptoms, primary care practitioners direct targeted diagnostic and treatment attention at both disorders.

Box 3 – Approach to identify and manage co‐occurring depression and insomnia*

---

CBTi = cognitive behavioural therapy for insomnia. * If both disorders are present, clinicians may recommend either concurrent or sequential treatment approaches with targeted treatments for both conditions.

Box 4 – Improvement in average Insomnia Severity Index scores (95% CI) during cognitive behaviour therapy for insomnia in 455 patients with chronic insomnia*

---

Adapted with permission from Sweetman et al.49
* There were no differences in insomnia improvements between patients with no/low depression, moderate depression and severe depression.