Role of Sleep in Depressive Disorders and the Potential Therapeutic Role of Short-Term Sleep Deprivation and Light Therapy: A Review

Introduction

Globally, about 280 million people, representing 3.8% of the world’s population, are estimated to have depression. The prevalence of common mental disorders is on the rise globally, particularly in lower-income countries, due to the lack of receiving effective treatments. Depression is also about 50% more common among women [1].

Depression, clinically referred to as major depressive disorder (MDD) as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), is a mood disorder characterized by persistent feeling of sadness, loss of interest or pleasure, and a variety of physical and emotional problems that significantly impair daily functioning. Individuals experiencing depression often display additional symptoms, such as changes in appetite or weight, fatigue, feelings of worthlessness, difficulty concentrating, and recurrent thoughts of death or suicide [2]. A diagnosis of MDD is typically considered when these symptoms persist for at least 2 weeks and represent a change from previous functioning [3]. Another symptom is the disruption in sleep patterns [4]. About 90% of patients have concerns about their sleep quality [4]. This fact shows that sleep can have an important effect on the clinical presentation of depressive disorders.

Depressive disorders encompass a range of conditions, including MDD, dysthymia (persistent depressive disorder), and bipolar disorder, among others. These conditions are diagnosed based on criteria outlined in the DSM-5. The essential component of bipolar affective disorder also involves depressive episodes. Bipolar affective disorder comprises alternating periods of lowered mood and manic states, thereby sharing certain aspects of patient management in both conditions, MDD and bipolar affective disorder [2].

The treatment of depressive disorders involves a combination of pharmacological and non-pharmacological interventions. Pharmacological treatments include the use of antidepressants, such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants, among others [4]. Non-pharmacological treatments encompass psychotherapy approaches, such as cognitive-behavioral therapy, interpersonal therapy, and other modalities designed to address the underlying cognitive and emotional aspects of depression [5]. In addition, research is being conducted on alternative treatment methods that would support or improve the effects of conventional therapy. Sleep deprivation and bright light therapy are two of them.

The aim of this review is to elucidate how important sleep’s role in depressive disorders is and to encourage clinicians to consider alternative methods of treatment related to it, such as light therapy and sleep deprivation.

Role of Sleep in Depressive Disorders

ANXIETY:

A study on a group of 3294 community-dwelling adults tested whether poor global sleep can be a mediator, and to what degree, of the prospective bidirectional anxiety-depression relationship [8]. The study group partook in 3 measurements of generalized anxiety disorder (GAD) and MDD at the baseline (T1), 9 years later (T2), and another 9 years later (T3). There was also 1 measurement of the quality of sleep at the study’s midpoint (T2). The results showed that higher MDD and GAD severity at the beginning predicted lower quality of sleep; and vice versa, poor sleep predicted higher GAD and MDD at the end. Furthermore, low quality of sleep explained 41% of the association between T1 GAD and T3 MDD, and 11% of the association between T1 MDD and T3 GAD. The authors explained those correlations in a few ways. First, there are similar risk factors for MDD, GAD, and sleep disturbances. For example, repetitive negative thinking patterns, which occur in MDD and GAD, can be exacerbated by insomnia; and vice versa, good quality of sleep can be hard to achieve with co-occurring negative thinking [8]. Finally, sleep issues over time also lead to higher vulnerability to stress, a risk factor for anxiety and depression [8].

CHRONIC INFLAMMATION:

It is proven that individuals with depression have higher levels of inflammation markers [9]. Even after 11 years, as the results of the next study demonstrated, levels of the inflammatory markers C-reactive protein and interleukin 6 were increased above and beyond concurrent depression, other health problems, or demographic factors [9]. Authors explained that relation by the overall poor sleep quality [9]. The low-grade chronic inflammation can also be induced over time by the long duration of sleep [7]. A large Indonesian study including 19 675 respondents indicated that this can be the mediator between sleep and depressive symptoms [7].

EMOTIONAL DYSREGULATION:

A study of a group of adults with MDD focused on the relationship between sleep and emotional dysregulation [10]. The results showed that lower sleep quality implicated worse emotional dysregulation. The authors presented a few possible explanations. First, poor sleep quality can disrupt prefrontal functions, such as cognitive control, an important part of emotional regulation. On the other hand, the components of emotional-cognitive dysfunction, namely limited coping strategies and lack of emotional recognition, can increase the risk of insomnia [10]. Authors also summoned up neurobiological theory, saying that emotional and behavioral regulation are controlled by the prefrontal cortex and the amygdala, which can explain the co-occurrence of emotional dysfunctions and sleep disturbances [10]. The results of another study correspond with that finding, showing that poor quality of sleep plays a large role in difficulties in disengaging attention from negative stimuli and developing mood disorders [7].

COGNITIVE DECLINE:

A study reports that one of the major impairments for individuals with depression can be a cognitive decline, especially among older adults, proving that the association between cognitive decline and depression in this group of patients is significant, independent of many confounders [6]. The researchers also showed that sleep partially mediated this relation, and the highest mediation rate, of 14.6%, was for daytime dysfunction. Sleep disturbance and subjective sleep quality were next [6].

IMPACT OF INDIVIDUAL SLEEP CHARACTERISTICS:

Among the various sleep characteristics, 3 characteristics stand out as having the greatest impact: quality, duration, and regularity.

The quality of sleep seems to have the strongest influence. As shown above, it can mediate most of the above-mentioned correlations. Sleep quality also corresponds with a higher prevalence of depression and can exacerbate other symptoms [7]. It also has a significant association with depressive symptoms among young adults with other serious mental illnesses [11].

Although the duration of sleep had a rather weaker association than sleep quality, studies showed that individuals with longer sleep had a higher risk of depression [7]. The duration of sleep also plays a role in the chronic inflammation process, which occurs among depressed individuals, as previously mentioned [5,10].

A study on a group of adolescents without mental disorders examined whether sleep regularity on school days, weekends, and holidays has an effect on depressive symptoms or general mental health [12]. The results showed that it has, depending on the kind of days. On weekdays, irregular sleep was associated with more depressive symptoms, which was correlated with sleep disturbances and daytime sleepiness and their interactions with school-specific stressors. On weekends, lower regularity of sleep induced worse overall mental health, and on holidays, it was related to neither of those variables [12].

BELIEFS ABOUT SLEEP:

Interestingly, the last sleep-related factor, which has a great effect on individuals with depression, is not associated with any pathophysiological processes. One study showed that patients with unhelpful beliefs about sleep, regardless of its objective quality, reported experiencing worse sleep quality and worse mood upon waking and tended to endorse sleep difficulties [13]. They also did not notice the variations in their sleep quality. On the other hand, individuals who reported longer sleep also tended to report better quality of it, in agreement with the sleep myth that “the more, the better” [13].

Alternative Treatment Methods

BRIGHT LIGHT THERAPY:

Bright light therapy is used in psychiatry as a treatment of choice for seasonal affective disorder [16]. Nonetheless, in recent years, the use of this non-pharmacological treatment method extended to other disorders, such as non-seasonal MDD, bipolar depression [17], and sleep disorders [18].

Despite the discovery of the positive effects of light therapy on various psychiatric conditions many years ago, its mechanism remains not fully known. However, the hypothesis says that light influences the suprachiasmatic nucleus, which is a region in the hypothalamus that controls circadian rhythms through the eye and the retinohypothalamic tract. It also suppresses melatonin secretion [18] and modulates serotonin secretion [14].

Depressive disorders are often associated with disturbances of circadian rhythms [19], which influence sleep propensity, alertness, and productivity in patients. Previously mentioned rhythms are associated with external day-night cycles affected by environmental factors, of which the light-dark cycle is the most important. Light exposure is known to influence circadian rhythms, and this is where light therapy comes, as it modifies light exposure patterns and therefore reduces sleep disruption, which contributes to a therapeutic effect [20].

Light therapy sessions take place daily and at home, through exposure to bright fluorescent light emitted by a light box. The standard protocol for depression consists of white light (intensity of 10 000 lux) used for 30 min a day in the morning [14]. Adverse effects that can occur are headaches, nausea, dizziness, tired eyes, insomnia, and early morning awakening, and hypomania in patients with bipolar disorder. Nevertheless, they are considered minor and usually last only for a few days [17].

As it is considered to be safe, well tolerated, and inexpensive, bright light therapy is used in MDD as monotherapy or in addition to pharmacological treatment [21], which often leads to better and accelerated clinical response [17]. According to one study, based on the Montgomery-Asberg Depression Rating Scale, bright light in monotherapy combined with fluoxetine in patients with MDD showed effectiveness in improving depression severity [22].

Another study conducted on patients with bipolar depression treated with antidepressants pointed out increased and accelerated therapeutic response in the bright light therapy group after 4 and 8 weeks of combined therapy, which was based on the Montgomery-Asberg Depression Rating Scale, Hamilton Depression Rating Scale, Clinical Global Impression Scale, and Quality of Life Scale scores measured at baseline, 4 weeks, and the end of the trial [23].

Sleep disturbances are some of the most common symptoms in patients with depressive disorders. A Chinese randomized controlled trial conducted on 93 patients with MDD over the course of 5 weeks showed that bright light therapy led to the improvement in subjective sleep timing, in comparison with the placebo dim red light group. However, the actigraphic parameters for the 2 groups were not significantly different [24].

Lastly, one study noted that some factors, such as poor drug response, different treatment regimens, duration of bright light therapy, and daylight variability, can impact the effectiveness of bright light therapy, which should be taken into consideration in future research [25].

SLEEP DEPRIVATION:

Many patients with depression seeking treatment do not respond sufficiently to medications, and even for those who do, it takes several weeks to achieve optimal therapeutic effects. This critical latency period is associated with an elevated risk of suicidal behaviour. Therefore, prioritizing the identification of rapid treatment options for alleviating depressive symptoms is crucial in clinical psychiatric research [26]. This is where sleep deprivation may prove to be useful, as it is reported to minimize depressive symptoms overnight, although it can often be a transitory effect [26].

Sleep deprivation is a very useful therapy for patients not responding to classical treatment, because of its symptom improvement duration that lasts 24 h [27]. It is defined as a period of imposed wakefulness, total or partial, in relation to a circadian cycle. Sleep deprivation has been accepted as a treatment for major depressive episodes [15].

Various treatment methods have been used, varying in the frequency, timing, and length of administered sleep deprivation cycles. There are various types of sleep deprivation: total sleep deprivation, in which patients stay awake for about 36 h in 1 cycle; partial sleep deprivation, in which patients are limited to 4 to 5 h of sleep; and sleep phase advance and sleep phase delay, which adjust the sleep time following a total sleep deprivation cycle [28]. The added complexity revolves around deciding whether sleep deprivation is used as a standalone treatment or as part of a comprehensive intervention that includes other chronotherapeutic or psychopharmacologic components [29].

The mechanisms underlying the potential antidepressant effect of sleep deprivation are not yet well understood. It is considered that it modulates homeostatic and circadian processes of sleep [30]. Sleep deprivation may play a role in shifting the window of inducible synaptic plasticity to a more optimal time, compensating for attenuated synaptic strength during proper wake periods and causing mood improvement [15].

The efficiency of sleep deprivation therapy is estimated at approximately 40% to 60%, even in treatment-refractory patients [26,27,31]. Furthermore, the outcomes could be improved depending on certain conditions. According to one study, some patients can experience a notable improvement in depressive symptoms while being in a highly controlled laboratory environment [32]. Studies have also documented increased response rates when sleep deprivation is complemented by adjunctive pharmacotherapy [29].

One study reports that there is a risk of a manic state occurring in patients with bipolar depression [26]. The switch rate was 5.5% among patients with bipolar affective disorder. Insufficient data have been obtained to draw conclusive findings on mood switching in patients with unipolar depression [26].

In one systematic review, participants universally shared positive experiences. Some individuals reported a rapid but short-lived antidepressant effect, while others described enduring benefits, such as improved sleep and diurnal rhythms. Negative experiences were minimal, mostly associated with disappointment over inadequate or transient responses [26], as well as tiredness, headache, poor concentration, and transient memory. However, another study presented cases of adverse events such as hypomania, increase in psychotic symptoms, or suicidality [15].

Sleep deprivation therapy is very promising, but further studies are required to determine the precise effects of sleep deprivation on patients with depressive episodes.

Future Directions

Sleep disturbances are some of the most common symptoms of depressive disorders. The quality and duration of sleep influence the risk of developing depression, severity of depression, emotional regulation, deterioration of cognitive functions, and level of general inflammation, and are mediators in the anxiety-depression relationship. This proves the importance of sleep and its large role in the course of depressive disorders. Beliefs about sleep can influence the mood and attitude of patients, and therefore also the course of therapy. These facts should not be ignored during therapy courses, considering their huge impact on subjective results.

Lack of response to conventional methods of depression treatment is still a therapeutic problem and prompts the search for new methods. Light therapy can be effective as monotherapy or in combination with antidepressants in patients with unipolar and bipolar depression. It also has minor and mild adverse effects. Further studies should be focused on determining precise clinical and patient-valued outcomes and selecting groups that will benefit most from this therapy. Sleep deprivation appears even more promising due to its rapid and significant positive effects on patients with depression. However, it has the risk of causing mania in patients with bipolar disorder. Further studies should gather certain data regarding the risk of mood switching in patients with unipolar depression who use sleep deprivation, as it is still not determined.

Conclusions

Sleep disturbances are some of the most common symptoms of depressive disorder and play a large role in the course of depressive disorders. The quality and duration of sleep can have an impact on the severity of depression, as well as be a mediator in relationships between depressive disorders and other depressive manifestations or co-occurring disorders. Also, beliefs about sleep have an effect in these processes. The problem of lack of response to conventional methods of depression treatment leads to the research for new methods. Light therapy can be effective in monotherapy or combined with antidepressants for patients with mono- and bipolar depression. It also has little and mild adverse effects. Sleep deprivation seems to be even more promising, due to its fast positive effects; however, there is a risk of inducing mania in patients with bipolar disorder. Further studies should be focused on determining the precise effect of these new methods.