David Baxter PhD
Late Founder
Exploring the Relationship Between Insomnia and Depression
by W. Vaughn McCall, MD, MS
Medscape Neurology & Neurosurgery. 2008
10/15/2008
The relationship between sleep and depression is complex, as insomnia has been observed to be both a risk factor for and a consequence of depression. Epidemiologic studies indicate that as many as 70% of patients with a psychiatric disorder also complain of insomnia.[1] In one survey of 7954 respondents, psychiatric disorders were evidenced in 40.4% of those who had insomnia, 46.5% of those who had hypersomnia, and 16.4% of those who had no sleep complaints (P < .001).[2] Polysomnographic studies indicate that patients with depression may experience any of the following abnormal sleep patterns: increased time to sleep onset, reduction of total sleep time, increased sleep fragmentation with increases in wake time after sleep onset, decreased slow-wave sleep associated with shortened rapid eye movement (REM) sleep latency, and increased REM sleep time during the early part of the night in the most severely depressed patients.[3] As discussed here, the relationship between insomnia and depression can be considered according to the timing of the appearance of each disorder's symptoms. Any information that can be gained about which disorder supersedes or coincides with the other will play a role in developing optimal treatment strategies.
Insomnia as a Precursor of Depression
It can be difficult to distinguish between the occurrence of primary insomnia or insomnia as a symptom of an underlying psychiatric disorder. Insomnia has been demonstrated to be a risk factor for major depressive disorder (MDD), dysthymic disorder, and bipolar disorder.[3,4] One sleep survey found that more than 40% of patients reported symptoms of insomnia before the development of a mood disorder.[5] Another study found that unresolved insomnia increases the odds of developing a new psychiatric disorder over the course of 1 year, as demonstrated by the fact that only 1.7% of patients with no sleep complaint developed a new depressive disorder, while 5.8% of patients with insomnia developed a new depressive disorder (P < .05).[2] Some evidence has demonstrated that treating the underlying symptoms of insomnia may provide beneficial effects toward reducing or preventing depression.[6] Thus, it is tempting to predict that aggressive treatment of insomnia could, in some cases, help prevent the occurrence of depressive disorders. However, this would require additional study because other data have suggested that the use of hypnotics themselves may contribute to the incidence of insomnia.[7]
Concurrent Incidence of Insomnia and Depression
Although insomnia is not one of the criteria required for a diagnosis of MDD, dysthymia, mania, or generalized anxiety disorder, insomnia is often described as a symptom associated with these conditions.[3] The concurrence of insomnia and depression increases the complexity of diagnosing and treating patients. It may be possible to differentiate between depression-related insomnia and primary insomnia by identifying particularly severe daytime symptoms typical of depression, such as persistent depressed mood and suicidality, suggesting that primary insomnia is, in many cases, a diagnosis of exclusion.[8]
The occurrence of concomitant sleep disturbances and depression has been observed to contribute to poorer health-related quality-of-life measures, which may include different aspects of physical functioning, such as limitations due to physical health (e.g., bodily pain, general health, vitality, and social functioning) and limitations due to emotional problems and mental health.[9] Insomnia has also been identified as a risk factor for suicide in depressed patients.[10] The observation of disrupted sleep patterns and electroencephalogram (EEG) changes in suicidal patients has been replicated repeatedly. A role for serotonin in both sleep disorders and suicide has been suggested because of observations that low levels of serotonin are often found in patients who have attempted or completed suicide, and serotonin plays an important role in the onset and maintenance of sleep.[11]
Persistent Insomnia Following Resolution of Depressive Symptoms
Insomnia is often one of the last symptoms to improve following successful treatment of depression, and, if not addressed, can lead to a relapse of depressive symptoms. Insomnia has been found to be present before relapse of depressive symptoms in 56.2% of cases.[5] Following treatment with antidepressants, most patients will demonstrate residual depressive symptoms, including almost half with some observance of sleep disruption.[12] Continued treatment and eventual resolution of the associated sleep disorder should help delay or prevent recurrence of depression; however, more research is needed to fully support this concept.
Management of Insomnia Concomitant With Depression
Concomitant insomnia and depression present a unique set of challenges for treatment. This is demonstrated particularly by the fact that sleep can be disrupted with the use of many different antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, or nonselective monoamine oxidase inhibitors. As a result, sleep-management strategies need to be added to the treatment regimen.[4] When treating persistent insomnia, pharmacologic treatments should be used if the patients will benefit from the rapid onset of medications, while continuing to pursue the more gradual, long-term solutions of cognitive-behavioral therapy and sleep-hygiene interventions.
Nonpharmacologic Treatment
Nonpharmacologic treatment of insomnia is reserved for chronic insomnia. Generally, nonpharmacologic treatment has fewer side effects compared with pharmacologic treatment. Nonpharmacologic treatments for primary insomnia include recommended changes to diet and lifestyle, as well as stimulus-control therapy, paradoxical-intention therapy, relaxation therapy, cognitive-behavioral therapy, sleep-restriction therapy, and improvements in sleep hygiene.[3,13] Although these treatment options have been used extensively for primary insomnia, their efficacy in the context of depression has been largely unexplored. Some evidence suggests that improvements in sleep resulting from implementation of a cognitive-behavioral therapy program can indirectly cause positive effects on patients with psychiatric disorders.[14] Additional research is needed regarding the combination of cognitive-behavioral therapy and antidepressant medication.[4,14]
Pharmacologic Treatment
Some evidence exists for the use of a combination of antidepressants and benzodiazepines (BZDs), non-benzodiazepine receptor agonists (zolpidem, eszopiclone), or trazodone to effectively manage insomnia and the associated depressive symptoms.[4] Adding clonazepam to fluoxetine for patients with depression who were experiencing treatment-associated insomnia resulted in improvements in anxiety and insomnia, in addition to modest reduction of some core symptoms of depression, within the first 21 days of treatment.[6] Adverse events, including sedation (usually mild), nausea, diarrhea, headache, dry mouth, decreased appetite, and delayed ejaculation, were similar for combination therapy and fluoxetine alone. A 3-month replication of this study found similar improvements in insomnia, but the improvements in the symptoms of anxiety and core symptoms of depression were not observed.[15] In another study of patients with depression and insomnia treated with SSRIs, zolpidem given at bedtime was associated with longer sleep times, better sleep quality, and reduced awakenings, as compared with placebo given at bedtime.[16] Incidence rates of adverse events were similar between zolpidem- and placebo-treated groups, with headaches as the most frequently reported treatment-emergent adverse event in both groups. In another study, patients with insomnia and MDD treated with open-label fluoxetine were randomly assigned to receive either eszopiclone 3 mg or placebo at bedtime. This study demonstrated significantly greater decreases in sleep latency and wake time after sleep onset (WASO) and increases in total sleep time, sleep quality, and depth of sleep over the 8-week study period in those patients receiving eszopiclone. The incidence of potentially treatment-related adverse events was higher in the eszopiclone group compared with placebo, with both groups most commonly experiencing unpleasant taste, headache, nausea, dry mouth, and somnolence.[17] In depressed patients with insomnia, trazodone significantly increased total sleep time, sleep efficiency index, sleep continuity index, and percentage of stages 3 and 4 sleep, while decreasing the number of awakenings, stage shifts, and percentage of stage 1 sleep compared with the baseline measurements. In this study, adverse events were minimal during the treatment period with trazodone, with 1 subject experiencing mild indigestion and 2 others experiencing mild daytime sedation.[18]
Summary
A complex relationship exists between insomnia and depressive disorders. Increased emphasis should be placed on treating insomnia in depression because it is a risk factor for depression. Insomnia also plays an important role in the course and severity of the depressive episode, and persistent insomnia is a risk factor for depressive relapse. Treatment strategies should address both depressive symptoms and insomnia and should consider use of both pharmacologic and nonpharmacologic strategies.
References
by W. Vaughn McCall, MD, MS
Medscape Neurology & Neurosurgery. 2008
10/15/2008
The relationship between sleep and depression is complex, as insomnia has been observed to be both a risk factor for and a consequence of depression. Epidemiologic studies indicate that as many as 70% of patients with a psychiatric disorder also complain of insomnia.[1] In one survey of 7954 respondents, psychiatric disorders were evidenced in 40.4% of those who had insomnia, 46.5% of those who had hypersomnia, and 16.4% of those who had no sleep complaints (P < .001).[2] Polysomnographic studies indicate that patients with depression may experience any of the following abnormal sleep patterns: increased time to sleep onset, reduction of total sleep time, increased sleep fragmentation with increases in wake time after sleep onset, decreased slow-wave sleep associated with shortened rapid eye movement (REM) sleep latency, and increased REM sleep time during the early part of the night in the most severely depressed patients.[3] As discussed here, the relationship between insomnia and depression can be considered according to the timing of the appearance of each disorder's symptoms. Any information that can be gained about which disorder supersedes or coincides with the other will play a role in developing optimal treatment strategies.
Insomnia as a Precursor of Depression
It can be difficult to distinguish between the occurrence of primary insomnia or insomnia as a symptom of an underlying psychiatric disorder. Insomnia has been demonstrated to be a risk factor for major depressive disorder (MDD), dysthymic disorder, and bipolar disorder.[3,4] One sleep survey found that more than 40% of patients reported symptoms of insomnia before the development of a mood disorder.[5] Another study found that unresolved insomnia increases the odds of developing a new psychiatric disorder over the course of 1 year, as demonstrated by the fact that only 1.7% of patients with no sleep complaint developed a new depressive disorder, while 5.8% of patients with insomnia developed a new depressive disorder (P < .05).[2] Some evidence has demonstrated that treating the underlying symptoms of insomnia may provide beneficial effects toward reducing or preventing depression.[6] Thus, it is tempting to predict that aggressive treatment of insomnia could, in some cases, help prevent the occurrence of depressive disorders. However, this would require additional study because other data have suggested that the use of hypnotics themselves may contribute to the incidence of insomnia.[7]
Concurrent Incidence of Insomnia and Depression
Although insomnia is not one of the criteria required for a diagnosis of MDD, dysthymia, mania, or generalized anxiety disorder, insomnia is often described as a symptom associated with these conditions.[3] The concurrence of insomnia and depression increases the complexity of diagnosing and treating patients. It may be possible to differentiate between depression-related insomnia and primary insomnia by identifying particularly severe daytime symptoms typical of depression, such as persistent depressed mood and suicidality, suggesting that primary insomnia is, in many cases, a diagnosis of exclusion.[8]
The occurrence of concomitant sleep disturbances and depression has been observed to contribute to poorer health-related quality-of-life measures, which may include different aspects of physical functioning, such as limitations due to physical health (e.g., bodily pain, general health, vitality, and social functioning) and limitations due to emotional problems and mental health.[9] Insomnia has also been identified as a risk factor for suicide in depressed patients.[10] The observation of disrupted sleep patterns and electroencephalogram (EEG) changes in suicidal patients has been replicated repeatedly. A role for serotonin in both sleep disorders and suicide has been suggested because of observations that low levels of serotonin are often found in patients who have attempted or completed suicide, and serotonin plays an important role in the onset and maintenance of sleep.[11]
Persistent Insomnia Following Resolution of Depressive Symptoms
Insomnia is often one of the last symptoms to improve following successful treatment of depression, and, if not addressed, can lead to a relapse of depressive symptoms. Insomnia has been found to be present before relapse of depressive symptoms in 56.2% of cases.[5] Following treatment with antidepressants, most patients will demonstrate residual depressive symptoms, including almost half with some observance of sleep disruption.[12] Continued treatment and eventual resolution of the associated sleep disorder should help delay or prevent recurrence of depression; however, more research is needed to fully support this concept.
Management of Insomnia Concomitant With Depression
Concomitant insomnia and depression present a unique set of challenges for treatment. This is demonstrated particularly by the fact that sleep can be disrupted with the use of many different antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, or nonselective monoamine oxidase inhibitors. As a result, sleep-management strategies need to be added to the treatment regimen.[4] When treating persistent insomnia, pharmacologic treatments should be used if the patients will benefit from the rapid onset of medications, while continuing to pursue the more gradual, long-term solutions of cognitive-behavioral therapy and sleep-hygiene interventions.
Nonpharmacologic Treatment
Nonpharmacologic treatment of insomnia is reserved for chronic insomnia. Generally, nonpharmacologic treatment has fewer side effects compared with pharmacologic treatment. Nonpharmacologic treatments for primary insomnia include recommended changes to diet and lifestyle, as well as stimulus-control therapy, paradoxical-intention therapy, relaxation therapy, cognitive-behavioral therapy, sleep-restriction therapy, and improvements in sleep hygiene.[3,13] Although these treatment options have been used extensively for primary insomnia, their efficacy in the context of depression has been largely unexplored. Some evidence suggests that improvements in sleep resulting from implementation of a cognitive-behavioral therapy program can indirectly cause positive effects on patients with psychiatric disorders.[14] Additional research is needed regarding the combination of cognitive-behavioral therapy and antidepressant medication.[4,14]
Pharmacologic Treatment
Some evidence exists for the use of a combination of antidepressants and benzodiazepines (BZDs), non-benzodiazepine receptor agonists (zolpidem, eszopiclone), or trazodone to effectively manage insomnia and the associated depressive symptoms.[4] Adding clonazepam to fluoxetine for patients with depression who were experiencing treatment-associated insomnia resulted in improvements in anxiety and insomnia, in addition to modest reduction of some core symptoms of depression, within the first 21 days of treatment.[6] Adverse events, including sedation (usually mild), nausea, diarrhea, headache, dry mouth, decreased appetite, and delayed ejaculation, were similar for combination therapy and fluoxetine alone. A 3-month replication of this study found similar improvements in insomnia, but the improvements in the symptoms of anxiety and core symptoms of depression were not observed.[15] In another study of patients with depression and insomnia treated with SSRIs, zolpidem given at bedtime was associated with longer sleep times, better sleep quality, and reduced awakenings, as compared with placebo given at bedtime.[16] Incidence rates of adverse events were similar between zolpidem- and placebo-treated groups, with headaches as the most frequently reported treatment-emergent adverse event in both groups. In another study, patients with insomnia and MDD treated with open-label fluoxetine were randomly assigned to receive either eszopiclone 3 mg or placebo at bedtime. This study demonstrated significantly greater decreases in sleep latency and wake time after sleep onset (WASO) and increases in total sleep time, sleep quality, and depth of sleep over the 8-week study period in those patients receiving eszopiclone. The incidence of potentially treatment-related adverse events was higher in the eszopiclone group compared with placebo, with both groups most commonly experiencing unpleasant taste, headache, nausea, dry mouth, and somnolence.[17] In depressed patients with insomnia, trazodone significantly increased total sleep time, sleep efficiency index, sleep continuity index, and percentage of stages 3 and 4 sleep, while decreasing the number of awakenings, stage shifts, and percentage of stage 1 sleep compared with the baseline measurements. In this study, adverse events were minimal during the treatment period with trazodone, with 1 subject experiencing mild indigestion and 2 others experiencing mild daytime sedation.[18]
Summary
A complex relationship exists between insomnia and depressive disorders. Increased emphasis should be placed on treating insomnia in depression because it is a risk factor for depression. Insomnia also plays an important role in the course and severity of the depressive episode, and persistent insomnia is a risk factor for depressive relapse. Treatment strategies should address both depressive symptoms and insomnia and should consider use of both pharmacologic and nonpharmacologic strategies.
References
- Ohayon MM, Shapiro CM, Kennedy SH. Differentiating DSM-IV anxiety and depressive disorders in the general population: comorbidity and treatment consequences. Can J Psychiatry. 2000;45:166-172.
- Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? JAMA. 1989;262:1479-1484.
- Becker PM. Treatment of sleep dysfunction and psychiatric disorders. Curr Treatment Options Neurol. 2006;8:367-375.
- Thase ME. Depression and sleep: pathophysiology and treatment. Dialogues Clin Neurosci. 2006;8:217-226.
- Ohayon MM, Roth T. Place of chronic insomnia in the course of depressive and anxiety disorders. J Psychiatric Res. 2003;37:9-15.
- Londborg PD, Smith WT, Glaudin V, Painter JR. Short-term cotherapy with clonazepam and fluoxetine: anxiety, sleep disturbance and core symptoms of depression. J Affect Disord. 2000;61:73-79.
- Kripke DF. Greater incidence of depression with hypnotic use than with placebo. BMC Psychiatry. 2007;7:42.
- Moul DE, Nofzinger EA, Pilkonis PA, Houck PR, Miewald JM, Buysse DJ. Symptom reports in severe chronic insomnia. Sleep. 2002;25:548-558.
- Hatoum HT, Kong SX, Kania CM, Wong JM, Mendelson WB. Insomnia, health-related quality of life and healthcare resource consumption. A study of managed-care organisation enrollees. Pharmacoeconomics. 1998;14:629-637.
- Fawcett J, Scheftner WA, Fogg L, et al. Time-related predictors of suicide in major affective disorder. Am J Psychiatry. 1990;147:1189-1194.
- Singareddy RK, Balon R. Sleep and suicide in psychiatric patients. Ann Clin Psychiatry. 2001;13:93-101.
- Nierenberg AA, Keefe BR, Leslie VC, et al. Residual symptoms in depressed patients who respond acutely to fluoxetine. J Clin Psychiatry. 1999;60:221-225.
- Ringdahl EN, Pereira SL, Delzell JE Jr. Treatment of primary insomnia. J Am Board Fam Pract. 2004;17:212-219.
- Smith MT, Huang MI, Manber R. Cognitive behavior therapy for chronic insomnia occurring within the context of medical and psychiatric disorders. Clin Psychol Rev. 2005;25:559-592.
- Smith WT, Londborg PD, Glaudin V, Painter JR. Is extended clonazepam cotherapy of fluoxetine effective for outpatients with major depression? J Affect Disord. 2002;70:251-259.
- Asnis GM, Chakraburtty A, DuBoff EA, et al. Zolpidem for persistent insomnia in SSRI-treated depressed patients. J Clin Psychiatry. 1999;60:668-676.
- Fava M, McCall WV, Krystal A, et al. Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder. Biol Psychiatry. 2006;59:1052-1060.
- Kaynak H, Kaynak D, Gozukirmizi E, Guilleminault C. The effects of trazodone on sleep in patients treated with stimulant antidepressants. Sleep Med. 2004;5:15-20.
