User login
Bright light therapy for bipolar depression
Bright light therapy (BLT) refers to the use of bright light to treat symptoms of depression. BLT was initially prescribed as a treatment for patients with seasonal affective disorder.1 It was later found helpful for nonseasonal depression,2 premenstrual dysphoric disorder, postpartum depression, and phase shift circadian disorders, including for patients with dementia whose cognitive function improved after treatment with BLT.3 More recent studies suggest year-round benefit for nonseasonal depression.2 The American Psychiatric Association practice guidelines for the treatment of depression list BLT as an alternative and/or addition to pharmacologic and psychological treatment.4 BLT also may be beneficial for patients who are in the depressive phase of bipolar illness.
This article describes the evidence, rationale for use, mechanism of action, benefits, and safety profile of BLT for treating patients with bipolar depression.
Circadian rhythm disruption in bipolar disorder
Clinical manifestation. Patients with bipolar disorder (BD) spend more time in depression than in mania.5 Sleep disturbance is a core symptom of BD; patients typically have little need for sleep during a manic episode, and excess sleepiness during a depressive episode. Sleep complaints can be both precipitating factors and consequences of mood disorders. Patients with seasonal depression have excess sleepiness and weight gain in the winter followed by hypomanic-like symptoms in the spring, including decreased need for sleep and weight loss with psychomotor activation. In a recent review of sleep problems in patients with BD, Steinan et al6 reported that 20% of patients with euthymic mood in bipolar disorder experience a sleep disorder. Circadian disruption and “eveningness” (being more active during the evening) have been associated with mood episodes, functional impairment, poor quality of life, and treatment resistance.7-10
Pathophysiology. Existing hypotheses for the biological mechanism underlying dysregulation of circadian rhythm in BD include changes in melatonin levels, expression of melatonin receptors in the CNS, and daily cortisol profiles.11 Genetic evidence also links circadian rhythm dysregulation with BD. Two polymorphisms on the circadian locomotor output cycles kaput (CLOCK) gene that control circadian rhythm—aryl hydrocarbon receptor nuclear translocator-like (ARNTL) and timeless circadian clock (TIMELESS)—have been linked to lithium responsiveness in BD.12 In addition, Per2, Cry1, and Rev-Erbα expression—all components of the circadian clock—have been found to increase individual susceptibility to the therapeutic effects of lithium in mice.13 In addition, circadian rhythm dysregulation is associated with metabolic problems encountered by patients with BD, including weight gain, diabetes mellitus, and cardiovascular disease.14
Rationale for use
Regulation of a patient’s circadian rhythm disruption is a potential treatment for BD. Hashimoto et al15 demonstrated that midday bright light exposure can phase advance and increase the amplitude of nocturnal melatonin production in healthy individuals. Morning light therapy has been shown to increase blood serotonin throughout the day in both healthy individuals and in patients with nonseasonal depression; the effect was apparent with light intensities as low as 50 lux.16 Lithium may exert its therapeutic effect through its influence on the retino-hypothalamic-pineal tract and thus its effect on melatonin secretion.17
BLT is a logical choice to treat the depression phase of BD when exposure to sunlight is not feasible due to geographical location, season, or other factor. For patients who live in areas that receive frequent sunshine, an outside stroll for half an hour will likely achieve similar benefit to BLT.
The precise mechanism of action of BLT for bipolar depression has not yet been determined. It may be attributed to a phase-resetting effect via melanopsin and the suprachiasmatic nucleus (Box18-24).
Box
Bright light therapy: How it works
The mechanism of action of bright light therapy is yet to be elucidated. The suprachiasmatic nucleus (SCN) in the hypothalamus is the center of circadian rhythm regulation and receives direct input from the retina through the retinohypothalamic tract.18 Melanopsin, a short-wavelength, light-sensitive G-protein–coupled receptor located in human retinal ganglion cells, is known to transduce short-wavelength light signals into neural signals.19 Since melanopsin is primarily responsible for resetting the timing of the SCN, suppressing pineal gland melatonin secretion and improving alertness and electroencephalogram-derived correlates of arousal,20 short-wavelength light with a low light intensity might be a better stimulator for melanopsin-containing retinal ganglion cells and the behaviors mediated via this photoreceptor system.21,22 Whether the antidepressant effect of light is also related to its alerting property is unclear.23 However, the acute alerting and performance-enhancing effects of light are increasingly taken into account for the design of indoor light standards in office environments.24 Response to light therapy is thus attributed to its phase-resetting effect.
Continue to: BLT for BD...
BLT for BD: What’s the evidence?
Several studies and case reports have evaluated the use of BLT for bipolar depression. The number of participants in these studies is small, and there is no uniformity of methodology or patient selection.
Dauphinais et al (2012)25 randomly assigned 44 patients with bipolar depression to BLT or a high-density or low-density negative ion generator for 8 weeks. They reported no difference in outcome between the various groups (50% vs 55.6%, remission and response rate). Only one patient in each group showed a switch to hypomania.
Carmadese et al (2015)26 reported an open-label study of adjunctive BLT in 31 difficult-to-treat patients with depression (16 unipolar and 15 bipolar). Significant improvement was noted within 3 weeks and was sustained in 1 patient with bipolar depression 5 weeks after cessation of BLT.
Papatheodorou and Kutcher (1995)27 treated 7 adolescents with bipolar depression with adjunctive BLT (10,000 lux twice per day). Three patients showed a marked response (>70% decrease from baseline Beck Depression Inventory and Symptom Check List scores). Two patients had a moderate response (40% to 47% decrease) and 2 patients obtained mild to no response. There were no reported adverse effects.
Benedetti et al (2014)28 studied 141 patients with treatment-resistant bipolar depression. Approximately one-quarter (23%) had a history of attempted suicide, and 83% had a history of drug resistance. The authors found a combination of total sleep deprivation, BLT, and lithium rapidly decreased suicidality and improved patients’ depressive symptoms.
Liebenluft et al (1995)29 administered 13 trials of BLT to 9 patients with rapid-cycling BD during a 3-month period. Five patients received the treatment in the morning, 5 around midday, and 3 in the evening. Patients who received BLT at midday had the best outcome, while 3 of the 5 patients who received morning BLT developed unstable mood. The authors recommended titrating the duration of light exposure so that patients could skip a treatment if their mood was trending toward hypomania.
Sit et al (2007)30 evaluated BLT in a case series of 9 women with bipolar I or II disorder in the depression phase. Patients were exposed to 50 lux of red light for 2 weeks, and then they received 7,000 lux BLT for 15, 30, and 45 minutes daily for 2 weeks (4 patients received morning light and 5 received midday light). Mood was assessed using the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement and the Mania Rating Scale. Of the 4 patients receiving morning BLT, one patient had a full response and the other 3 developed hypomania. Of the 5 patients who received midday BLT, 2 achieved full response, 2 showed early improvement but required a dose increase, and one remained depressed but had a full response when she was switched to morning BLT.
Tseng et al (2016)31 reported a meta-analysis of BLT for bipolar depression that included a total of 567 patients from 11 studies. They reported significant improvement with BLT alone or in combination with antidepressants or total sleep deprivation. They also reported significant improvement with BLT in 130 patients who were not receiving other treatments. There was no difference in the frequency of mood shifts between patients on BLT alone or in combination with other modalities. The authors reported no mood shift in any of the patients receiving concurrent mood stabilizers. They also reported no difference with the color of light, gender, or duration of illness.
Yorguner et al (2017)32 conducted a 2-week randomized, single-blind study of BLT as an add-on treatment for 32 patients with bipolar depression. Patients were randomly assigned to BLT or dim light, which they were administered each morning for 30 mins for 2 weeks. Sixteen patients who received BLT showed a significantly greater reduction in Hamilton Depression Rating Scale scores (mean score of 24 at baseline down to 12) compared with 16 patients who received dim light (mean score of 24 at baseline down to 18). The authors also reported remission in 4 out of 4 patients who had seasonal depression, compared with 3 out of 12 who did not have seasonal depression (the other 9 showed response but not remission).
Zhou et al (2018)33 conducted a multi-center, randomized, single-blind clinical trial of 63 patients with bipolar depression. Thirty-three patients received morning BLT, and 30 received dim red light therapy (control group). The authors reported a significantly higher response rate in the BLT group (78%) compared with the control group (43%).
Sit et al (2018)34 conducted a 6-week randomized, double-blind, placebo-controlled trial of BLT vs dim red light in patients with bipolar I or II depression. Twenty-three patients were administered 7,000 lux bright white light, and 23 patients received 50 lux dim red light, at midday 5 days a week. The light dose was increased by 15 minutes every week up to 60 minutes by Week 4, unless the patient achieved remission. Patients were maintained on their usual medications, which included mood stabilizers and/or antidepressants. At Week 6, the group randomized to BLT had a significantly higher remission rate (68%) compared with patients who received dim red light (22%). Improvement was noted by Week 4. Patients receiving BLT also had significantly fewer depressive symptoms, and no mood polarity switch was noted.
Prescribing bright light therapy
Light box selection criteria. When selecting a light box or related BLT treatment apparatus, the Center for Environmental Therapeutics recommends consideration of the following factors35:
- clinical efficacy
- ocular and dermatologic safety
- visual comfort.
Selecting a dose. The dose received is determined by the intensity emitted from the light source, distance from the light box, and duration of exposure.36 Begin with midday light therapy between 12 noon and 2
Monitor for adverse effects. Generally, BLT is well tolerated.37 Adverse effects are rare; the most common ones include headache, eyestrain, nausea, and agitation.38 One study found no adverse ocular effects from light therapy after 5 years of treatment.39 Adverse effects tend to remit spontaneously or after dose reduction.35 Evening administration of BLT may increase the incidence of sleep disturbances.40 Like other biologic treatments for bipolar depression, BLT can precipitate manic/hypomanic and mixed states in susceptible patients, although the light dose can be titrated against emergent symptoms of hypomania.41
Bottom Line
Evidence suggests that bright light therapy is an effective, well tolerated, and affordable adjunct treatment for bipolar depression. Exposure to 5,000 to 7,000 lux around noon for 15 to 60 minutes will enhance the remission rate.
Related Resource
Mostert M, Dubovsky S. When bipolar treatment fails: what’s your next step? Current Psychiatry. 2008;7(1):39-46.
Drug Brand Name
Lithium • Eskalith, Lithobid
1. Pjrek E, Winkler D, Stastny J, et al. Bright light therapy in seasonal affective disorder--does it suffice? Eur Neuropsychopharmacol. 2004.14(4):347-351.
2. Al-Karawi D, Jubair L. Bright light therapy for nonseasonal depression: meta-analysis of clinical trials. J Affect Disord. 2016;198:64-71.
3. Sekiguchi H, Iritani S, Fujita K. Bright light therapy for sleep disturbance in dementia is most effective for mild to moderate Alzheimer’s type dementia: a case series. Psychogeriatrics, 2017;17(5):275-281.
4. Gelenberg AJ, Freeman MP, Markowitz JC, et al. Practice guideline for the treatment of patients with major depressive disorder, third edition. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf American Psychiatric Association. 2010. Accessed August, 10, 2017.
5. Kupka RW, Altshuler LL, Nolen WA, et al. Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder. Bipolar Disord. 2007;9(5):531-535.
6. Steinan MK, Krane-Gartiser K, Morken G, et al. Sleep problems in euthymic bipolar disorders: a review of clinical studies. Current Psychiatry Reviews. 2015;11:235-243.
7. Cudney LE, Frey BN, Streiner D, et al. Biological rhythms are independently associated with quality of life in bipolar disorder. Int J Bipolar Disord. 2016;4(1):9.
8. Duarte FA, Cardoso TA, Campos MT, et al. Biological rhythms in bipolar and depressive disorders: a community study with drug-naive young adults. J Affect Disord, 2015;186:145-148.
9. Pinho M, Sehmbi M, Cudney LE, et al. The association between biological rhythms, depression, and functioning in bipolar disorder: a large multi-center study. Acta Psychiatr Scand. 2015:133(2);102-108.
10. Ng TH, Chung KF, Lee CT, et al. Eveningness and its associated impairments in remitted bipolar disorder. Behav Sleep Med. 2016:14(6):650-664.
11. Wu YH, Ursinus J, Zahn JN, et al. Alterations of melatonin receptors MT1 and MT2 in the hypothalamic suprachiasmatic nucleus during depression. J Affect Disord, 2013:148(2-3):357-367.
12. Rybakowski JK, Dmitrzak-Weglar M, Kliwicki S, et al. Polymorphism of circadian clock genes and prophylactic lithium response. Bipolar Disord. 2014;16(2):151-158.
13. Schnell A, Sandrelli F, Ranc V, et al. Mice lacking circadian clock components display different mood-related behaviors and do not respond uniformly to chronic lithium treatment. Chronobiol Int. 2015;32(8):1075-1089.
14. Kim Y, Santos R, Gage FH, et al. Molecular mechanisms of bipolar disorder: progress made and future challenges. Front Cell Neurosci. 2017;11:30.
15. Hashimoto S, Kohsaka M, Nakamura K. Midday exposure to bright light changes the circadian organization of plasma melatonin rhythm in humans. Neurosci Lett. 1997;221(2-3):
89-92.
16. Rao ML, Müller-Oerlinghausen B, Mackert A, et al. The influence of phototherapy on serotonin and melatonin in non-seasonal depression. Pharmacopsychiatry.1990;23(3):155-158.
17. Moreira J, Geoffroy PA. Lithium and bipolar disorder: impacts from molecular to behavioural circadian rhythms. Chronobiol Int. 2016;33(4):351-373.
18. Oldham MA, Ciraulo DA. Bright light therapy for depression: a review of its effects on chronobiology and the autonomic nervous system. Chronobiol Int. 2014;31(3):305-319.
19. Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science. 2002;295(5557):1070-1073.
20. Peirson S, Foster RG. Melanopsin: another way of signaling light. Neuron. 2006;49(3):331-339.
21. Anderson JL, Glod CA, Dai J, et al. Lux vs. wavelength in light treatment of seasonal affective disorder. Acta Psychiatr Scand. 2009;120(3):203-212.
22. Wirz-Justice A, Graw P, Kräuchi K, et al. Effect of light on unmasked circadian rhythms in winter depression. In: Wetterberg L, ed. Light and biological rhythms in man. Oxford, United Kingdom:Pergamon Press;1993:385-393.
23. Cajochen C. Alerting effects of light. Sleep Med Rev. 2007;11(6):453-464.
24. Aries MBC. Human lighting demands: healthy lighting in an office environment. Eindhoven, Eindhoven University Press. 2005;158. doi:10.6100/IR594257.
25. Dauphinais DR, Rosenthal JZ, Terman M, et al. Controlled trial of safety and efficacy of bright light therapy vs. negative air ions in patients with bipolar depression. Psychiatry Res. 2012;196(1):57-61.
26. Camardese G, Leone B, Serrani R, et al. Augmentation of light therapy in difficult-to-treat depressed patients: an open-label trial in both unipolar and bipolar patients. Neuropsychiatr Dis Treat. 2015;11:2331-2338.
27. Papatheodorou G, Kutcher S. The effect of adjunctive light therapy on ameliorating breakthrough depressive symptoms in adolescent-onset bipolar disorder.
J Psychiatry Neurosci. 1995;20(3):226-232.
28. Benedetti F, Riccaboni R, Locatelli C, et al. Rapid treatment response of suicidal symptoms to lithium, sleep deprivation, and light therapy (chronotherapeutics) in drug-resistant bipolar depression. J Clin Psychiatry. 2014;75(2):133-140.
29. Liebenluft E, Turner EH, Felman-Naim S, et al. Light therapy in patients with rapid cycling bipolar disorder: preliminary results. Psychopharmacol Bull. 1995;31(4):
705-710.
30. Sit DK, Wisner KL, Hanusa BH, et al. Light therapy for bipolar disorder: a case series in women. Bipolar Disord. 2007;9(8):918-927.
31. Tseng PT, Chen YW, Tu KY, et al. Light therapy in the treatment of patients with bipolar depression: a meta-analytic study. Eur Neuropsychopharmacol. 2016;26(6):
1037-1047.
32. Yorguner KN, Bulut NS, Carkaxhiu BG, et al. Efficacy of bright light therapy in bipolar depression. Psychiatry Res. 2017;260:432-438.
33. Zhou TH, Dang WM, Ma YT, et al. Clinical efficacy, onset time and safety of bright light therapy in acute bipolar depression as an adjunctive therapy: a randomized controlled trial. J Affect Disord. 2018;227:90-96.
34. Sit DK, McGowan J, Wiltrout C, et al. Adjunctive bright light therapy for bipolar depression: a randomized double-blind placebo-controlled trial. Am J Psychiatry. 2018;175(2):
131-139.
35. Center for Environmental Therapeutics. https://www.cet.org/. Center for Environmental Therapeutics. Accessed November 15, 2017.
36. Lam RW, Levitt AJ. Canadian consensus guidelines for the treatment of seasonal affective disorder. https://mdsc.ca/documents/Consumer%20and%20Family%20Support/CCG_on_Seasonal_Affective_Disorder.pdf. 1999. Accessed August 2, 2017.
37. Terman M, Terman JS. Bright light therapy: side effects and benefits across the symptom spectrum. J Clin Psychiatry. 1999; 60(11):799-808;quiz 809.
38. Labbate LA, et al. Side effects induced by bright light treatment for seasonal affective disorder. J Clin Psychiatry. 1994; 55(5):189-191.
39. Gallin PF, et al. Ophthalmologic examination of patients with seasonal affective disorder, before and after bright light therapy. Am J Ophthalmol. 1995;119(2):202-210.
40. Chan PK, Lam RW, Perry KF. Mania precipitated by light therapy for patients with SAD. J Clin Psychiatry. 1994;55(10):454.
41. Kripke DF. Timing of phototherapy and occurrence of mania. Biol Psychiatry. 1991; 29(11):1156-1157.
Bright light therapy (BLT) refers to the use of bright light to treat symptoms of depression. BLT was initially prescribed as a treatment for patients with seasonal affective disorder.1 It was later found helpful for nonseasonal depression,2 premenstrual dysphoric disorder, postpartum depression, and phase shift circadian disorders, including for patients with dementia whose cognitive function improved after treatment with BLT.3 More recent studies suggest year-round benefit for nonseasonal depression.2 The American Psychiatric Association practice guidelines for the treatment of depression list BLT as an alternative and/or addition to pharmacologic and psychological treatment.4 BLT also may be beneficial for patients who are in the depressive phase of bipolar illness.
This article describes the evidence, rationale for use, mechanism of action, benefits, and safety profile of BLT for treating patients with bipolar depression.
Circadian rhythm disruption in bipolar disorder
Clinical manifestation. Patients with bipolar disorder (BD) spend more time in depression than in mania.5 Sleep disturbance is a core symptom of BD; patients typically have little need for sleep during a manic episode, and excess sleepiness during a depressive episode. Sleep complaints can be both precipitating factors and consequences of mood disorders. Patients with seasonal depression have excess sleepiness and weight gain in the winter followed by hypomanic-like symptoms in the spring, including decreased need for sleep and weight loss with psychomotor activation. In a recent review of sleep problems in patients with BD, Steinan et al6 reported that 20% of patients with euthymic mood in bipolar disorder experience a sleep disorder. Circadian disruption and “eveningness” (being more active during the evening) have been associated with mood episodes, functional impairment, poor quality of life, and treatment resistance.7-10
Pathophysiology. Existing hypotheses for the biological mechanism underlying dysregulation of circadian rhythm in BD include changes in melatonin levels, expression of melatonin receptors in the CNS, and daily cortisol profiles.11 Genetic evidence also links circadian rhythm dysregulation with BD. Two polymorphisms on the circadian locomotor output cycles kaput (CLOCK) gene that control circadian rhythm—aryl hydrocarbon receptor nuclear translocator-like (ARNTL) and timeless circadian clock (TIMELESS)—have been linked to lithium responsiveness in BD.12 In addition, Per2, Cry1, and Rev-Erbα expression—all components of the circadian clock—have been found to increase individual susceptibility to the therapeutic effects of lithium in mice.13 In addition, circadian rhythm dysregulation is associated with metabolic problems encountered by patients with BD, including weight gain, diabetes mellitus, and cardiovascular disease.14
Rationale for use
Regulation of a patient’s circadian rhythm disruption is a potential treatment for BD. Hashimoto et al15 demonstrated that midday bright light exposure can phase advance and increase the amplitude of nocturnal melatonin production in healthy individuals. Morning light therapy has been shown to increase blood serotonin throughout the day in both healthy individuals and in patients with nonseasonal depression; the effect was apparent with light intensities as low as 50 lux.16 Lithium may exert its therapeutic effect through its influence on the retino-hypothalamic-pineal tract and thus its effect on melatonin secretion.17
BLT is a logical choice to treat the depression phase of BD when exposure to sunlight is not feasible due to geographical location, season, or other factor. For patients who live in areas that receive frequent sunshine, an outside stroll for half an hour will likely achieve similar benefit to BLT.
The precise mechanism of action of BLT for bipolar depression has not yet been determined. It may be attributed to a phase-resetting effect via melanopsin and the suprachiasmatic nucleus (Box18-24).
Box
Bright light therapy: How it works
The mechanism of action of bright light therapy is yet to be elucidated. The suprachiasmatic nucleus (SCN) in the hypothalamus is the center of circadian rhythm regulation and receives direct input from the retina through the retinohypothalamic tract.18 Melanopsin, a short-wavelength, light-sensitive G-protein–coupled receptor located in human retinal ganglion cells, is known to transduce short-wavelength light signals into neural signals.19 Since melanopsin is primarily responsible for resetting the timing of the SCN, suppressing pineal gland melatonin secretion and improving alertness and electroencephalogram-derived correlates of arousal,20 short-wavelength light with a low light intensity might be a better stimulator for melanopsin-containing retinal ganglion cells and the behaviors mediated via this photoreceptor system.21,22 Whether the antidepressant effect of light is also related to its alerting property is unclear.23 However, the acute alerting and performance-enhancing effects of light are increasingly taken into account for the design of indoor light standards in office environments.24 Response to light therapy is thus attributed to its phase-resetting effect.
Continue to: BLT for BD...
BLT for BD: What’s the evidence?
Several studies and case reports have evaluated the use of BLT for bipolar depression. The number of participants in these studies is small, and there is no uniformity of methodology or patient selection.
Dauphinais et al (2012)25 randomly assigned 44 patients with bipolar depression to BLT or a high-density or low-density negative ion generator for 8 weeks. They reported no difference in outcome between the various groups (50% vs 55.6%, remission and response rate). Only one patient in each group showed a switch to hypomania.
Carmadese et al (2015)26 reported an open-label study of adjunctive BLT in 31 difficult-to-treat patients with depression (16 unipolar and 15 bipolar). Significant improvement was noted within 3 weeks and was sustained in 1 patient with bipolar depression 5 weeks after cessation of BLT.
Papatheodorou and Kutcher (1995)27 treated 7 adolescents with bipolar depression with adjunctive BLT (10,000 lux twice per day). Three patients showed a marked response (>70% decrease from baseline Beck Depression Inventory and Symptom Check List scores). Two patients had a moderate response (40% to 47% decrease) and 2 patients obtained mild to no response. There were no reported adverse effects.
Benedetti et al (2014)28 studied 141 patients with treatment-resistant bipolar depression. Approximately one-quarter (23%) had a history of attempted suicide, and 83% had a history of drug resistance. The authors found a combination of total sleep deprivation, BLT, and lithium rapidly decreased suicidality and improved patients’ depressive symptoms.
Liebenluft et al (1995)29 administered 13 trials of BLT to 9 patients with rapid-cycling BD during a 3-month period. Five patients received the treatment in the morning, 5 around midday, and 3 in the evening. Patients who received BLT at midday had the best outcome, while 3 of the 5 patients who received morning BLT developed unstable mood. The authors recommended titrating the duration of light exposure so that patients could skip a treatment if their mood was trending toward hypomania.
Sit et al (2007)30 evaluated BLT in a case series of 9 women with bipolar I or II disorder in the depression phase. Patients were exposed to 50 lux of red light for 2 weeks, and then they received 7,000 lux BLT for 15, 30, and 45 minutes daily for 2 weeks (4 patients received morning light and 5 received midday light). Mood was assessed using the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement and the Mania Rating Scale. Of the 4 patients receiving morning BLT, one patient had a full response and the other 3 developed hypomania. Of the 5 patients who received midday BLT, 2 achieved full response, 2 showed early improvement but required a dose increase, and one remained depressed but had a full response when she was switched to morning BLT.
Tseng et al (2016)31 reported a meta-analysis of BLT for bipolar depression that included a total of 567 patients from 11 studies. They reported significant improvement with BLT alone or in combination with antidepressants or total sleep deprivation. They also reported significant improvement with BLT in 130 patients who were not receiving other treatments. There was no difference in the frequency of mood shifts between patients on BLT alone or in combination with other modalities. The authors reported no mood shift in any of the patients receiving concurrent mood stabilizers. They also reported no difference with the color of light, gender, or duration of illness.
Yorguner et al (2017)32 conducted a 2-week randomized, single-blind study of BLT as an add-on treatment for 32 patients with bipolar depression. Patients were randomly assigned to BLT or dim light, which they were administered each morning for 30 mins for 2 weeks. Sixteen patients who received BLT showed a significantly greater reduction in Hamilton Depression Rating Scale scores (mean score of 24 at baseline down to 12) compared with 16 patients who received dim light (mean score of 24 at baseline down to 18). The authors also reported remission in 4 out of 4 patients who had seasonal depression, compared with 3 out of 12 who did not have seasonal depression (the other 9 showed response but not remission).
Zhou et al (2018)33 conducted a multi-center, randomized, single-blind clinical trial of 63 patients with bipolar depression. Thirty-three patients received morning BLT, and 30 received dim red light therapy (control group). The authors reported a significantly higher response rate in the BLT group (78%) compared with the control group (43%).
Sit et al (2018)34 conducted a 6-week randomized, double-blind, placebo-controlled trial of BLT vs dim red light in patients with bipolar I or II depression. Twenty-three patients were administered 7,000 lux bright white light, and 23 patients received 50 lux dim red light, at midday 5 days a week. The light dose was increased by 15 minutes every week up to 60 minutes by Week 4, unless the patient achieved remission. Patients were maintained on their usual medications, which included mood stabilizers and/or antidepressants. At Week 6, the group randomized to BLT had a significantly higher remission rate (68%) compared with patients who received dim red light (22%). Improvement was noted by Week 4. Patients receiving BLT also had significantly fewer depressive symptoms, and no mood polarity switch was noted.
Prescribing bright light therapy
Light box selection criteria. When selecting a light box or related BLT treatment apparatus, the Center for Environmental Therapeutics recommends consideration of the following factors35:
- clinical efficacy
- ocular and dermatologic safety
- visual comfort.
Selecting a dose. The dose received is determined by the intensity emitted from the light source, distance from the light box, and duration of exposure.36 Begin with midday light therapy between 12 noon and 2
Monitor for adverse effects. Generally, BLT is well tolerated.37 Adverse effects are rare; the most common ones include headache, eyestrain, nausea, and agitation.38 One study found no adverse ocular effects from light therapy after 5 years of treatment.39 Adverse effects tend to remit spontaneously or after dose reduction.35 Evening administration of BLT may increase the incidence of sleep disturbances.40 Like other biologic treatments for bipolar depression, BLT can precipitate manic/hypomanic and mixed states in susceptible patients, although the light dose can be titrated against emergent symptoms of hypomania.41
Bottom Line
Evidence suggests that bright light therapy is an effective, well tolerated, and affordable adjunct treatment for bipolar depression. Exposure to 5,000 to 7,000 lux around noon for 15 to 60 minutes will enhance the remission rate.
Related Resource
Mostert M, Dubovsky S. When bipolar treatment fails: what’s your next step? Current Psychiatry. 2008;7(1):39-46.
Drug Brand Name
Lithium • Eskalith, Lithobid
Bright light therapy (BLT) refers to the use of bright light to treat symptoms of depression. BLT was initially prescribed as a treatment for patients with seasonal affective disorder.1 It was later found helpful for nonseasonal depression,2 premenstrual dysphoric disorder, postpartum depression, and phase shift circadian disorders, including for patients with dementia whose cognitive function improved after treatment with BLT.3 More recent studies suggest year-round benefit for nonseasonal depression.2 The American Psychiatric Association practice guidelines for the treatment of depression list BLT as an alternative and/or addition to pharmacologic and psychological treatment.4 BLT also may be beneficial for patients who are in the depressive phase of bipolar illness.
This article describes the evidence, rationale for use, mechanism of action, benefits, and safety profile of BLT for treating patients with bipolar depression.
Circadian rhythm disruption in bipolar disorder
Clinical manifestation. Patients with bipolar disorder (BD) spend more time in depression than in mania.5 Sleep disturbance is a core symptom of BD; patients typically have little need for sleep during a manic episode, and excess sleepiness during a depressive episode. Sleep complaints can be both precipitating factors and consequences of mood disorders. Patients with seasonal depression have excess sleepiness and weight gain in the winter followed by hypomanic-like symptoms in the spring, including decreased need for sleep and weight loss with psychomotor activation. In a recent review of sleep problems in patients with BD, Steinan et al6 reported that 20% of patients with euthymic mood in bipolar disorder experience a sleep disorder. Circadian disruption and “eveningness” (being more active during the evening) have been associated with mood episodes, functional impairment, poor quality of life, and treatment resistance.7-10
Pathophysiology. Existing hypotheses for the biological mechanism underlying dysregulation of circadian rhythm in BD include changes in melatonin levels, expression of melatonin receptors in the CNS, and daily cortisol profiles.11 Genetic evidence also links circadian rhythm dysregulation with BD. Two polymorphisms on the circadian locomotor output cycles kaput (CLOCK) gene that control circadian rhythm—aryl hydrocarbon receptor nuclear translocator-like (ARNTL) and timeless circadian clock (TIMELESS)—have been linked to lithium responsiveness in BD.12 In addition, Per2, Cry1, and Rev-Erbα expression—all components of the circadian clock—have been found to increase individual susceptibility to the therapeutic effects of lithium in mice.13 In addition, circadian rhythm dysregulation is associated with metabolic problems encountered by patients with BD, including weight gain, diabetes mellitus, and cardiovascular disease.14
Rationale for use
Regulation of a patient’s circadian rhythm disruption is a potential treatment for BD. Hashimoto et al15 demonstrated that midday bright light exposure can phase advance and increase the amplitude of nocturnal melatonin production in healthy individuals. Morning light therapy has been shown to increase blood serotonin throughout the day in both healthy individuals and in patients with nonseasonal depression; the effect was apparent with light intensities as low as 50 lux.16 Lithium may exert its therapeutic effect through its influence on the retino-hypothalamic-pineal tract and thus its effect on melatonin secretion.17
BLT is a logical choice to treat the depression phase of BD when exposure to sunlight is not feasible due to geographical location, season, or other factor. For patients who live in areas that receive frequent sunshine, an outside stroll for half an hour will likely achieve similar benefit to BLT.
The precise mechanism of action of BLT for bipolar depression has not yet been determined. It may be attributed to a phase-resetting effect via melanopsin and the suprachiasmatic nucleus (Box18-24).
Box
Bright light therapy: How it works
The mechanism of action of bright light therapy is yet to be elucidated. The suprachiasmatic nucleus (SCN) in the hypothalamus is the center of circadian rhythm regulation and receives direct input from the retina through the retinohypothalamic tract.18 Melanopsin, a short-wavelength, light-sensitive G-protein–coupled receptor located in human retinal ganglion cells, is known to transduce short-wavelength light signals into neural signals.19 Since melanopsin is primarily responsible for resetting the timing of the SCN, suppressing pineal gland melatonin secretion and improving alertness and electroencephalogram-derived correlates of arousal,20 short-wavelength light with a low light intensity might be a better stimulator for melanopsin-containing retinal ganglion cells and the behaviors mediated via this photoreceptor system.21,22 Whether the antidepressant effect of light is also related to its alerting property is unclear.23 However, the acute alerting and performance-enhancing effects of light are increasingly taken into account for the design of indoor light standards in office environments.24 Response to light therapy is thus attributed to its phase-resetting effect.
Continue to: BLT for BD...
BLT for BD: What’s the evidence?
Several studies and case reports have evaluated the use of BLT for bipolar depression. The number of participants in these studies is small, and there is no uniformity of methodology or patient selection.
Dauphinais et al (2012)25 randomly assigned 44 patients with bipolar depression to BLT or a high-density or low-density negative ion generator for 8 weeks. They reported no difference in outcome between the various groups (50% vs 55.6%, remission and response rate). Only one patient in each group showed a switch to hypomania.
Carmadese et al (2015)26 reported an open-label study of adjunctive BLT in 31 difficult-to-treat patients with depression (16 unipolar and 15 bipolar). Significant improvement was noted within 3 weeks and was sustained in 1 patient with bipolar depression 5 weeks after cessation of BLT.
Papatheodorou and Kutcher (1995)27 treated 7 adolescents with bipolar depression with adjunctive BLT (10,000 lux twice per day). Three patients showed a marked response (>70% decrease from baseline Beck Depression Inventory and Symptom Check List scores). Two patients had a moderate response (40% to 47% decrease) and 2 patients obtained mild to no response. There were no reported adverse effects.
Benedetti et al (2014)28 studied 141 patients with treatment-resistant bipolar depression. Approximately one-quarter (23%) had a history of attempted suicide, and 83% had a history of drug resistance. The authors found a combination of total sleep deprivation, BLT, and lithium rapidly decreased suicidality and improved patients’ depressive symptoms.
Liebenluft et al (1995)29 administered 13 trials of BLT to 9 patients with rapid-cycling BD during a 3-month period. Five patients received the treatment in the morning, 5 around midday, and 3 in the evening. Patients who received BLT at midday had the best outcome, while 3 of the 5 patients who received morning BLT developed unstable mood. The authors recommended titrating the duration of light exposure so that patients could skip a treatment if their mood was trending toward hypomania.
Sit et al (2007)30 evaluated BLT in a case series of 9 women with bipolar I or II disorder in the depression phase. Patients were exposed to 50 lux of red light for 2 weeks, and then they received 7,000 lux BLT for 15, 30, and 45 minutes daily for 2 weeks (4 patients received morning light and 5 received midday light). Mood was assessed using the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement and the Mania Rating Scale. Of the 4 patients receiving morning BLT, one patient had a full response and the other 3 developed hypomania. Of the 5 patients who received midday BLT, 2 achieved full response, 2 showed early improvement but required a dose increase, and one remained depressed but had a full response when she was switched to morning BLT.
Tseng et al (2016)31 reported a meta-analysis of BLT for bipolar depression that included a total of 567 patients from 11 studies. They reported significant improvement with BLT alone or in combination with antidepressants or total sleep deprivation. They also reported significant improvement with BLT in 130 patients who were not receiving other treatments. There was no difference in the frequency of mood shifts between patients on BLT alone or in combination with other modalities. The authors reported no mood shift in any of the patients receiving concurrent mood stabilizers. They also reported no difference with the color of light, gender, or duration of illness.
Yorguner et al (2017)32 conducted a 2-week randomized, single-blind study of BLT as an add-on treatment for 32 patients with bipolar depression. Patients were randomly assigned to BLT or dim light, which they were administered each morning for 30 mins for 2 weeks. Sixteen patients who received BLT showed a significantly greater reduction in Hamilton Depression Rating Scale scores (mean score of 24 at baseline down to 12) compared with 16 patients who received dim light (mean score of 24 at baseline down to 18). The authors also reported remission in 4 out of 4 patients who had seasonal depression, compared with 3 out of 12 who did not have seasonal depression (the other 9 showed response but not remission).
Zhou et al (2018)33 conducted a multi-center, randomized, single-blind clinical trial of 63 patients with bipolar depression. Thirty-three patients received morning BLT, and 30 received dim red light therapy (control group). The authors reported a significantly higher response rate in the BLT group (78%) compared with the control group (43%).
Sit et al (2018)34 conducted a 6-week randomized, double-blind, placebo-controlled trial of BLT vs dim red light in patients with bipolar I or II depression. Twenty-three patients were administered 7,000 lux bright white light, and 23 patients received 50 lux dim red light, at midday 5 days a week. The light dose was increased by 15 minutes every week up to 60 minutes by Week 4, unless the patient achieved remission. Patients were maintained on their usual medications, which included mood stabilizers and/or antidepressants. At Week 6, the group randomized to BLT had a significantly higher remission rate (68%) compared with patients who received dim red light (22%). Improvement was noted by Week 4. Patients receiving BLT also had significantly fewer depressive symptoms, and no mood polarity switch was noted.
Prescribing bright light therapy
Light box selection criteria. When selecting a light box or related BLT treatment apparatus, the Center for Environmental Therapeutics recommends consideration of the following factors35:
- clinical efficacy
- ocular and dermatologic safety
- visual comfort.
Selecting a dose. The dose received is determined by the intensity emitted from the light source, distance from the light box, and duration of exposure.36 Begin with midday light therapy between 12 noon and 2
Monitor for adverse effects. Generally, BLT is well tolerated.37 Adverse effects are rare; the most common ones include headache, eyestrain, nausea, and agitation.38 One study found no adverse ocular effects from light therapy after 5 years of treatment.39 Adverse effects tend to remit spontaneously or after dose reduction.35 Evening administration of BLT may increase the incidence of sleep disturbances.40 Like other biologic treatments for bipolar depression, BLT can precipitate manic/hypomanic and mixed states in susceptible patients, although the light dose can be titrated against emergent symptoms of hypomania.41
Bottom Line
Evidence suggests that bright light therapy is an effective, well tolerated, and affordable adjunct treatment for bipolar depression. Exposure to 5,000 to 7,000 lux around noon for 15 to 60 minutes will enhance the remission rate.
Related Resource
Mostert M, Dubovsky S. When bipolar treatment fails: what’s your next step? Current Psychiatry. 2008;7(1):39-46.
Drug Brand Name
Lithium • Eskalith, Lithobid
1. Pjrek E, Winkler D, Stastny J, et al. Bright light therapy in seasonal affective disorder--does it suffice? Eur Neuropsychopharmacol. 2004.14(4):347-351.
2. Al-Karawi D, Jubair L. Bright light therapy for nonseasonal depression: meta-analysis of clinical trials. J Affect Disord. 2016;198:64-71.
3. Sekiguchi H, Iritani S, Fujita K. Bright light therapy for sleep disturbance in dementia is most effective for mild to moderate Alzheimer’s type dementia: a case series. Psychogeriatrics, 2017;17(5):275-281.
4. Gelenberg AJ, Freeman MP, Markowitz JC, et al. Practice guideline for the treatment of patients with major depressive disorder, third edition. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf American Psychiatric Association. 2010. Accessed August, 10, 2017.
5. Kupka RW, Altshuler LL, Nolen WA, et al. Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder. Bipolar Disord. 2007;9(5):531-535.
6. Steinan MK, Krane-Gartiser K, Morken G, et al. Sleep problems in euthymic bipolar disorders: a review of clinical studies. Current Psychiatry Reviews. 2015;11:235-243.
7. Cudney LE, Frey BN, Streiner D, et al. Biological rhythms are independently associated with quality of life in bipolar disorder. Int J Bipolar Disord. 2016;4(1):9.
8. Duarte FA, Cardoso TA, Campos MT, et al. Biological rhythms in bipolar and depressive disorders: a community study with drug-naive young adults. J Affect Disord, 2015;186:145-148.
9. Pinho M, Sehmbi M, Cudney LE, et al. The association between biological rhythms, depression, and functioning in bipolar disorder: a large multi-center study. Acta Psychiatr Scand. 2015:133(2);102-108.
10. Ng TH, Chung KF, Lee CT, et al. Eveningness and its associated impairments in remitted bipolar disorder. Behav Sleep Med. 2016:14(6):650-664.
11. Wu YH, Ursinus J, Zahn JN, et al. Alterations of melatonin receptors MT1 and MT2 in the hypothalamic suprachiasmatic nucleus during depression. J Affect Disord, 2013:148(2-3):357-367.
12. Rybakowski JK, Dmitrzak-Weglar M, Kliwicki S, et al. Polymorphism of circadian clock genes and prophylactic lithium response. Bipolar Disord. 2014;16(2):151-158.
13. Schnell A, Sandrelli F, Ranc V, et al. Mice lacking circadian clock components display different mood-related behaviors and do not respond uniformly to chronic lithium treatment. Chronobiol Int. 2015;32(8):1075-1089.
14. Kim Y, Santos R, Gage FH, et al. Molecular mechanisms of bipolar disorder: progress made and future challenges. Front Cell Neurosci. 2017;11:30.
15. Hashimoto S, Kohsaka M, Nakamura K. Midday exposure to bright light changes the circadian organization of plasma melatonin rhythm in humans. Neurosci Lett. 1997;221(2-3):
89-92.
16. Rao ML, Müller-Oerlinghausen B, Mackert A, et al. The influence of phototherapy on serotonin and melatonin in non-seasonal depression. Pharmacopsychiatry.1990;23(3):155-158.
17. Moreira J, Geoffroy PA. Lithium and bipolar disorder: impacts from molecular to behavioural circadian rhythms. Chronobiol Int. 2016;33(4):351-373.
18. Oldham MA, Ciraulo DA. Bright light therapy for depression: a review of its effects on chronobiology and the autonomic nervous system. Chronobiol Int. 2014;31(3):305-319.
19. Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science. 2002;295(5557):1070-1073.
20. Peirson S, Foster RG. Melanopsin: another way of signaling light. Neuron. 2006;49(3):331-339.
21. Anderson JL, Glod CA, Dai J, et al. Lux vs. wavelength in light treatment of seasonal affective disorder. Acta Psychiatr Scand. 2009;120(3):203-212.
22. Wirz-Justice A, Graw P, Kräuchi K, et al. Effect of light on unmasked circadian rhythms in winter depression. In: Wetterberg L, ed. Light and biological rhythms in man. Oxford, United Kingdom:Pergamon Press;1993:385-393.
23. Cajochen C. Alerting effects of light. Sleep Med Rev. 2007;11(6):453-464.
24. Aries MBC. Human lighting demands: healthy lighting in an office environment. Eindhoven, Eindhoven University Press. 2005;158. doi:10.6100/IR594257.
25. Dauphinais DR, Rosenthal JZ, Terman M, et al. Controlled trial of safety and efficacy of bright light therapy vs. negative air ions in patients with bipolar depression. Psychiatry Res. 2012;196(1):57-61.
26. Camardese G, Leone B, Serrani R, et al. Augmentation of light therapy in difficult-to-treat depressed patients: an open-label trial in both unipolar and bipolar patients. Neuropsychiatr Dis Treat. 2015;11:2331-2338.
27. Papatheodorou G, Kutcher S. The effect of adjunctive light therapy on ameliorating breakthrough depressive symptoms in adolescent-onset bipolar disorder.
J Psychiatry Neurosci. 1995;20(3):226-232.
28. Benedetti F, Riccaboni R, Locatelli C, et al. Rapid treatment response of suicidal symptoms to lithium, sleep deprivation, and light therapy (chronotherapeutics) in drug-resistant bipolar depression. J Clin Psychiatry. 2014;75(2):133-140.
29. Liebenluft E, Turner EH, Felman-Naim S, et al. Light therapy in patients with rapid cycling bipolar disorder: preliminary results. Psychopharmacol Bull. 1995;31(4):
705-710.
30. Sit DK, Wisner KL, Hanusa BH, et al. Light therapy for bipolar disorder: a case series in women. Bipolar Disord. 2007;9(8):918-927.
31. Tseng PT, Chen YW, Tu KY, et al. Light therapy in the treatment of patients with bipolar depression: a meta-analytic study. Eur Neuropsychopharmacol. 2016;26(6):
1037-1047.
32. Yorguner KN, Bulut NS, Carkaxhiu BG, et al. Efficacy of bright light therapy in bipolar depression. Psychiatry Res. 2017;260:432-438.
33. Zhou TH, Dang WM, Ma YT, et al. Clinical efficacy, onset time and safety of bright light therapy in acute bipolar depression as an adjunctive therapy: a randomized controlled trial. J Affect Disord. 2018;227:90-96.
34. Sit DK, McGowan J, Wiltrout C, et al. Adjunctive bright light therapy for bipolar depression: a randomized double-blind placebo-controlled trial. Am J Psychiatry. 2018;175(2):
131-139.
35. Center for Environmental Therapeutics. https://www.cet.org/. Center for Environmental Therapeutics. Accessed November 15, 2017.
36. Lam RW, Levitt AJ. Canadian consensus guidelines for the treatment of seasonal affective disorder. https://mdsc.ca/documents/Consumer%20and%20Family%20Support/CCG_on_Seasonal_Affective_Disorder.pdf. 1999. Accessed August 2, 2017.
37. Terman M, Terman JS. Bright light therapy: side effects and benefits across the symptom spectrum. J Clin Psychiatry. 1999; 60(11):799-808;quiz 809.
38. Labbate LA, et al. Side effects induced by bright light treatment for seasonal affective disorder. J Clin Psychiatry. 1994; 55(5):189-191.
39. Gallin PF, et al. Ophthalmologic examination of patients with seasonal affective disorder, before and after bright light therapy. Am J Ophthalmol. 1995;119(2):202-210.
40. Chan PK, Lam RW, Perry KF. Mania precipitated by light therapy for patients with SAD. J Clin Psychiatry. 1994;55(10):454.
41. Kripke DF. Timing of phototherapy and occurrence of mania. Biol Psychiatry. 1991; 29(11):1156-1157.
1. Pjrek E, Winkler D, Stastny J, et al. Bright light therapy in seasonal affective disorder--does it suffice? Eur Neuropsychopharmacol. 2004.14(4):347-351.
2. Al-Karawi D, Jubair L. Bright light therapy for nonseasonal depression: meta-analysis of clinical trials. J Affect Disord. 2016;198:64-71.
3. Sekiguchi H, Iritani S, Fujita K. Bright light therapy for sleep disturbance in dementia is most effective for mild to moderate Alzheimer’s type dementia: a case series. Psychogeriatrics, 2017;17(5):275-281.
4. Gelenberg AJ, Freeman MP, Markowitz JC, et al. Practice guideline for the treatment of patients with major depressive disorder, third edition. https://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf American Psychiatric Association. 2010. Accessed August, 10, 2017.
5. Kupka RW, Altshuler LL, Nolen WA, et al. Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder. Bipolar Disord. 2007;9(5):531-535.
6. Steinan MK, Krane-Gartiser K, Morken G, et al. Sleep problems in euthymic bipolar disorders: a review of clinical studies. Current Psychiatry Reviews. 2015;11:235-243.
7. Cudney LE, Frey BN, Streiner D, et al. Biological rhythms are independently associated with quality of life in bipolar disorder. Int J Bipolar Disord. 2016;4(1):9.
8. Duarte FA, Cardoso TA, Campos MT, et al. Biological rhythms in bipolar and depressive disorders: a community study with drug-naive young adults. J Affect Disord, 2015;186:145-148.
9. Pinho M, Sehmbi M, Cudney LE, et al. The association between biological rhythms, depression, and functioning in bipolar disorder: a large multi-center study. Acta Psychiatr Scand. 2015:133(2);102-108.
10. Ng TH, Chung KF, Lee CT, et al. Eveningness and its associated impairments in remitted bipolar disorder. Behav Sleep Med. 2016:14(6):650-664.
11. Wu YH, Ursinus J, Zahn JN, et al. Alterations of melatonin receptors MT1 and MT2 in the hypothalamic suprachiasmatic nucleus during depression. J Affect Disord, 2013:148(2-3):357-367.
12. Rybakowski JK, Dmitrzak-Weglar M, Kliwicki S, et al. Polymorphism of circadian clock genes and prophylactic lithium response. Bipolar Disord. 2014;16(2):151-158.
13. Schnell A, Sandrelli F, Ranc V, et al. Mice lacking circadian clock components display different mood-related behaviors and do not respond uniformly to chronic lithium treatment. Chronobiol Int. 2015;32(8):1075-1089.
14. Kim Y, Santos R, Gage FH, et al. Molecular mechanisms of bipolar disorder: progress made and future challenges. Front Cell Neurosci. 2017;11:30.
15. Hashimoto S, Kohsaka M, Nakamura K. Midday exposure to bright light changes the circadian organization of plasma melatonin rhythm in humans. Neurosci Lett. 1997;221(2-3):
89-92.
16. Rao ML, Müller-Oerlinghausen B, Mackert A, et al. The influence of phototherapy on serotonin and melatonin in non-seasonal depression. Pharmacopsychiatry.1990;23(3):155-158.
17. Moreira J, Geoffroy PA. Lithium and bipolar disorder: impacts from molecular to behavioural circadian rhythms. Chronobiol Int. 2016;33(4):351-373.
18. Oldham MA, Ciraulo DA. Bright light therapy for depression: a review of its effects on chronobiology and the autonomic nervous system. Chronobiol Int. 2014;31(3):305-319.
19. Berson DM, Dunn FA, Takao M. Phototransduction by retinal ganglion cells that set the circadian clock. Science. 2002;295(5557):1070-1073.
20. Peirson S, Foster RG. Melanopsin: another way of signaling light. Neuron. 2006;49(3):331-339.
21. Anderson JL, Glod CA, Dai J, et al. Lux vs. wavelength in light treatment of seasonal affective disorder. Acta Psychiatr Scand. 2009;120(3):203-212.
22. Wirz-Justice A, Graw P, Kräuchi K, et al. Effect of light on unmasked circadian rhythms in winter depression. In: Wetterberg L, ed. Light and biological rhythms in man. Oxford, United Kingdom:Pergamon Press;1993:385-393.
23. Cajochen C. Alerting effects of light. Sleep Med Rev. 2007;11(6):453-464.
24. Aries MBC. Human lighting demands: healthy lighting in an office environment. Eindhoven, Eindhoven University Press. 2005;158. doi:10.6100/IR594257.
25. Dauphinais DR, Rosenthal JZ, Terman M, et al. Controlled trial of safety and efficacy of bright light therapy vs. negative air ions in patients with bipolar depression. Psychiatry Res. 2012;196(1):57-61.
26. Camardese G, Leone B, Serrani R, et al. Augmentation of light therapy in difficult-to-treat depressed patients: an open-label trial in both unipolar and bipolar patients. Neuropsychiatr Dis Treat. 2015;11:2331-2338.
27. Papatheodorou G, Kutcher S. The effect of adjunctive light therapy on ameliorating breakthrough depressive symptoms in adolescent-onset bipolar disorder.
J Psychiatry Neurosci. 1995;20(3):226-232.
28. Benedetti F, Riccaboni R, Locatelli C, et al. Rapid treatment response of suicidal symptoms to lithium, sleep deprivation, and light therapy (chronotherapeutics) in drug-resistant bipolar depression. J Clin Psychiatry. 2014;75(2):133-140.
29. Liebenluft E, Turner EH, Felman-Naim S, et al. Light therapy in patients with rapid cycling bipolar disorder: preliminary results. Psychopharmacol Bull. 1995;31(4):
705-710.
30. Sit DK, Wisner KL, Hanusa BH, et al. Light therapy for bipolar disorder: a case series in women. Bipolar Disord. 2007;9(8):918-927.
31. Tseng PT, Chen YW, Tu KY, et al. Light therapy in the treatment of patients with bipolar depression: a meta-analytic study. Eur Neuropsychopharmacol. 2016;26(6):
1037-1047.
32. Yorguner KN, Bulut NS, Carkaxhiu BG, et al. Efficacy of bright light therapy in bipolar depression. Psychiatry Res. 2017;260:432-438.
33. Zhou TH, Dang WM, Ma YT, et al. Clinical efficacy, onset time and safety of bright light therapy in acute bipolar depression as an adjunctive therapy: a randomized controlled trial. J Affect Disord. 2018;227:90-96.
34. Sit DK, McGowan J, Wiltrout C, et al. Adjunctive bright light therapy for bipolar depression: a randomized double-blind placebo-controlled trial. Am J Psychiatry. 2018;175(2):
131-139.
35. Center for Environmental Therapeutics. https://www.cet.org/. Center for Environmental Therapeutics. Accessed November 15, 2017.
36. Lam RW, Levitt AJ. Canadian consensus guidelines for the treatment of seasonal affective disorder. https://mdsc.ca/documents/Consumer%20and%20Family%20Support/CCG_on_Seasonal_Affective_Disorder.pdf. 1999. Accessed August 2, 2017.
37. Terman M, Terman JS. Bright light therapy: side effects and benefits across the symptom spectrum. J Clin Psychiatry. 1999; 60(11):799-808;quiz 809.
38. Labbate LA, et al. Side effects induced by bright light treatment for seasonal affective disorder. J Clin Psychiatry. 1994; 55(5):189-191.
39. Gallin PF, et al. Ophthalmologic examination of patients with seasonal affective disorder, before and after bright light therapy. Am J Ophthalmol. 1995;119(2):202-210.
40. Chan PK, Lam RW, Perry KF. Mania precipitated by light therapy for patients with SAD. J Clin Psychiatry. 1994;55(10):454.
41. Kripke DF. Timing of phototherapy and occurrence of mania. Biol Psychiatry. 1991; 29(11):1156-1157.
No laughing matter: Laughter is good psychiatric medicine
CASE REPORT: Laughter as therapy
Mrs. A is a 56-year-old married woman who has bipolar disorder. She has survived several suicide attempts. Her family history is positive for bipolar disorder and completed suicides.
After her most recent suicide attempt and a course of electroconvulsive therapy, Mrs. A recovered sufficiently to begin a spiritual journey that led her to practice a technique known as Laughter Yoga (Box) and, eventually, to become a Laughter Yoga instructor.
Mrs. A begins Laughter Yoga sessions by talking openly with students about her illness and the beneficial effects that laughter therapy has had on its course: She once had at least two major bipolar episodes a year, she explains, but has been in full remission for several years despite severe psychosocial stressors. In addition to practicing Laughter Yoga, Mrs. A is now maintained on a mood stabilizer that failed in the past to control her mood cycles.
Does laughter have a place in your practice?
It is said that laughter is good medicine—but is it good psychiatric medicine? Where might humor and laughter fit in the psychiatrist’s armamentarium? Is laughter physiologically beneficial to psychiatric patients? And are there adverse effects or contraindications to laughter in psychiatry? This article:
• reviews studies that have examined the anatomy, physiology, and psychology of humor and laughtera
• offers answers to the questions posed above (Table).
“Gelotology,” from the Greek “gelos,” laughter, is the science of laughter. The three components of humor and laughter are:
• the emotional component, which triggers emotions produced by a humorous situation
• the cognitive component, in which a person “gets it”
• the movement of facial, respiratory, and abdominal muscles.
Furthermore, tension and surprise are needed for laughter.
Theories about humor are varied
Philosophers since Plato have proposed theories of humor; modern theories of humor can be traced to Freud’s work.1 The psychoanalytic literature on humor focuses on the role of humor in sublimation of feelings of anger and hostility, while releasing affect in an economical way.
Erikson also wrote about the role of humor in a child’s developing superego, which helps resolve the conflict with maternal authority.2
In a comprehensive review of theories of humor, Krichtafovitch explains that cognitive theories address the role of incongruity and contrast in the induction of laughter, whereas social theories explore the roles of aggression, hostility, superiority, triumph, derision, and disparagement in humor and laughter. The effect of humor, Krichtafovitch explains, is to elevate the social status of the joker while the listener’s social status is lifted through his (her) ability to “get it.” Thus, humor plays a meaningful role in creating a bond between speaker and listener.3
The neuroanatomy of laughter
Here is some of what we have learned about mapping the brain to the basis of laughter:
• Consider a 16-year-old girl who underwent neurosurgery for intractable seizures. During surgery, various parts of the brain were stimulated to test for the focus of the seizures. She laughed every time the left frontal superior gyrus was stimulated. According to the report, she apparently laughed first, then made up a story that was funny to her.4
• Pseudobulbar affect—excessive, usually incongruent laughter, secondary to neurologic disease or traumatic brain injury—is an example of the biologic basis of laughter.
• Many functional brain imaging studies of laughter have been published.5 These studies show involvement of various regions of the brain in laughter, including the amygdala, hypothalamus, and temporal and cerebellar regions.
• Sex differences also have been noted in the neuroanatomy of laughter. Females activate the left prefrontal cortex more than males do, suggesting a greater degree of executive processing and language-based decoding. Females also exhibit greater activation of mesolimbic regions, including the nucleus accumbens, implying a greater reward network response.6
• Wild et al7 reported that separate cortical regions are responsible for the production of facial expressions that are emotionally driven (through laughter) and voluntary.
The physiology of laughter
Humans begin to laugh at approximately 4 months of age. Children laugh, on average, 400 times a day; adults do so an average of only 5 times a day.8 In addition:
• Tickling a baby induces her (him) to laugh, which, in turn, makes the parent laugh; a social bond develops during this playful exercise. This response is probably mediated by 5-HT1A receptors, which, when stimulated, induces the release of oxytocin, which facilitates social bonding.9
• Potent stimulation of 5-HT1A receptors through ingestion of 3,4-methylenedioxy-N-methylamphetamine (Ecstasy) leads to uncontrollable laughter and mirth.10
• Lower species are also known to enjoy humor. Mice emit a chirping sound when tickled, and laughter is contagious among monkeys.11
• Berk et al12,13 reported that, when 52 healthy men watched a funny video for 30 minutes, they had significantly higher activity of natural killer (NK) cells and higher levels of IgG, IgA, and IgM compared with men who watched an emotionally neutral documentary.
• Bennett et al14 showed that, in 33 healthy women, the harder the laughter, the higher the NK activity.
• Sugawara et al15 showed improved cardiovascular function in 17 healthy persons (age 23 to 42) who watched a 30-minute comedy video, compared with their cardiovascular function when they watched a documentary video of equal length.
• Svebak et al16 examined the effect of humor as measured by the Sense of Humor Survey on the survival rate of more then 53,000 adults in one county in Norway. They concluded that the higher the sense of humor score, the higher the odds ratio of surviving 7 years, compared with subjects who had a lower sense of humor.
Clinical studies of laughter
The Coping Humor Scale (CHS) and the Humor Response Scale (HRS) are the two most widely used tools to measure a person’s innate sense of humor (the CHS) and the ability to respond to a humorous situation (the HRS).17 Several studies about the effects of laughter on illness are notable:
• Laughter increased NK cell activity, lowered prorenin gene expression, and lowered the postprandial glucose level in 34 patients with diabetes, compared with 16 matched controls.18-21
• Clark et al studied the sense of humor of 150 patients with cardiac disease compared with 150 controls. They found that “people with heart disease responded less humorously to everyday life situations.” They generally laughed less, even in positive situations, and displayed more anger and hostility.22
• In his work on the salutatory effect of laughter on the experience of pain, Cousins described how he dealt with his painful arthritis by watching Marx Brothers movies23:
I made the joyous discovery that 10 minutes of genuine belly laughter had an anesthetic effect and would give me at least two hours of pain-free sleep… When the pain-killing effect of the laughter wore off, we would switch on the motion picture projector again and not infrequently, it would lead to another pain-free interval.
• Hearty laughter leads to pain relief, probably through the release of endorphins. Dunbar et al24 tested this hypothesis in a series of six experimental studies in the laboratory (watching videos) and in a naturalistic context (watching stage performances), using a change in pain threshold as an indirect measure of endorphin release. The results show that the pain threshold is significantly higher after laughter than in the control condition. This pain-tolerance effect is caused by the laughter itself, not simply because of a change in positive affect.
Laughter therapy for depression
Three studies have demonstrated the benefit of laughter therapy in depression:
• When Ko and Youn25 studied 48 geriatric depressed patients and 61 age-matched controls, they found a significantly lower Geriatric Depression Scale score and a better Pittsburgh Sleep Quality Index score in patients who had been exposed to four weekly laughter groups, compared with persons who had been exposed to a control group.
• Shahidi et al26 randomly assigned 60 community-dwelling female, geriatric, depressed patients to a laughter yoga group, an exercise group, and a control group. Laughter yoga and exercise were equally effective, and both were significantly superior to the control condition. The laughter yoga group scored significantly better than the other two groups on the Life Satisfaction Scale. The researchers concluded that, in addition to improved mood, patients who laugh experience increased life satisfaction.
• Fonzi et al27 summarized data on the neurophysiology of laughter and the effect of laughter on the hypothalamus-pituitary-adrenal axis. They noted that depression reduces the frequency of laughter and, inversely, laughter reduces the severity of depression. Laughter, they reported, also increases the connectivity of patients with people in their life, which further alleviates symptoms of depression.
Other therapeutic uses of laughter
Humor can strengthen the bond of the therapeutic relationship. Patients who laugh with their physicians are more likely to feel connected with them, follow their advice, and feel more satisfied with their encounter. One study found that primary care physicians who gave positive statements, spent more time with patients, and included humor or laughter during their visits lowered their risk of being sued for malpractice.28
Consider also the use of laughter in altering family dynamics in a therapeutic setting: Mr. and Mrs. B attend therapy in my practice to address a difficult situation with their adult children. One of them enables their children socially and financially; the other continually complains about this enabling. When the tension was high and the couple had reached an impasse during a visit, the therapist offered an anecdote from the 2006 motion picture Failure to Launch (in which a man lives in the security of his parents’ home even though he is in his 30s), that dissipated the hostility they had shown toward each other and toward their children. The couple was then able to proceed to conflict resolution.
Recommendations, caveats
If you are considering incorporating laughter into therapy, keep in mind that:
• you should ensure that the patient does not perceive humor as minimizing the seriousness of their problems
• humor can be a minefield if not used judiciously, or if used at all, around certain sensitive topics, such as race, ethnicity, religion, political affiliation, and sexual orientation
• the timing of humor is particularly essential for it to succeed in the context of a therapeutic relationship
• from a medical perspective, laughter in patients who are recovering from abdominal or other major surgery might compromise wound healing because of increased intra-abdominal pressure associated with laughing
• patients who have asthma, especially exercise-induced asthma, might be at risk of developing an acute asthmatic attack when they laugh very hard. Lebowitz et al29 demonstrated that laughter can have a negative effect on patients with chronic obstructive pulmonary disease.
It is advisable in some situations to avoid humor in psychotherapy, such as when the patient or family is hostile—because, as noted, they might perceive laughter and humor as an attempt to minimize the seriousness of their discontent.
Bottom Line
Humor and laughter are underutilized and underreported in therapy, in part because it is a nascent field of research. Laughter has social and physiologic benefits that can be used in the context of a therapeutic relationship to help patients with a variety of ailments, including depression, anxiety, and pain.
Related Resources
- Association for Applied and Therapeutic Humor. www.aath.org.
- Mora-Ripoll R. The therapeutic value of laughter in medicine. Altern Ther Health Med. 2010;16:56-64.
- Strean WB. Laughter prescription. Can Fam Physician. 2009;55:965-967.
Disclosure
Dr. Nasr reports no financial relationship with manufacturers of any products mentioned in this article or with manufacturers of competing products.
Acknowledgements
The author acknowledges the assistance of Francois E. Alouf, MD, for suggestions on topics to include in the article; John W. Crayton, MD, for reviewing the manuscript; and Burdette Wendt for assistance with the references.
1. Freud S, Strachey J, trans., ed. Jokes and their relation to the unconscious. New York, NY: W. W. Norton & Company; 1990.
2. Capps D. Mother, melancholia, and humor in Erik H. Erikson’s earliest writings. J Relig Health. 2008;47:415-432.
3. Krichtafovitch I. Humor theory. Parker, CO: Outskirts Press; 2006.
4. Fried I, Wilson CL, MacDonald KA, et al. Electric current stimulates laughter. Nature. 1998;12;391:650.
5. Bartolo A, Benuzzi F, Nocetti L, et al. Humor comprehension and appreciation: an FMRI study. J Cogn Neurosci. 2006;18:1789-1798.
6. Azim E, Mobbs D, Jo B, et al. Sex differences in brain activation elicited by humor. Proc Natl Acad Sci U S A. 2005;102:16496-16501.
7. Wild B, Rodden FA, Rapp A, et al. Humor and smiling: cortical regions selective for cognitive, affective, and volitional components. Neurology. 2006;66:887-893.
8. Freedman LW. Mosby’s complementary and alternative medicine. A research-based approach. St. Louis, MO: Mosby; 2004:24.
9. Lukas M, Toth I, Reber SO, et al. The neuropeptide oxytocin facilitates pro-social behavior and prevents social avoidance in rats and mice. Neuropsychopharmacology. 2011;36:
2159-2168.
10. Thompson MR, Callaghan PD, Hunt GE, et al. A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine (“ecstasy”). Neuroscience. 2007;146:509-514.
11. Ross MD, Owren MJ, Zimmermann E. The evolution of laughter in great apes and humans. Commun Integr Biol. 2010;3(2):191-194.
12. Berk LS, Tan SA, Fry WF, et al. Neuroendocrine and stress hormone changes during mirthful laughter. Am J Med Sci. 1989;298:390-396.
13. Berk LS, Felten DL, Tan SA, et al. Modulation of neuroimmune parameters during the eustress of humor-associated mirthful laughter. Altern Ther Health Med. 2001; 7:62-72,74-76.
14. Bennett MP, Zeller JM, Rosenberg L, et al. The effect of mirthful laughter on stress and natural killer cell activity. Altern Ther Health Med. 2003;9:38-45.
15. Sugawara J, Tarumi T, Tanaka H. Effect of mirthful laughter on vascular function. Am J Cardiol. 2010;106:856-859.
16. Svebak S, Romundstad S, Holmen J. A 7-year prospective study of sense of humor and mortality in an adult county population: the HUNT-2 study. Int J Psychiatry Med. 2010;40:125-146.
17. Martin RA. The Situational Humor Response Questionnaire (SHRQ) and Coping Humor Scale (CHS): a decade of research findings. Humor: International Journal of Humor Research. 1996;9(3-4):251-272.
18. Hayashi T, Urayama O, Hori M, et al. Laughter modulates prorenin receptor gene expression in patients with type 2 diabetes. J Psychosom Res. 2007;62:703-706.
19. Hayashi T, Murakami K. The effects of laughter on post-prandial glucose levels and gene expression in type 2 diabetic patients. Life Sci. 2009;85:185-187.
20. Takahashi K, Iwase M, Yamashita K, et al. The elevation of natural killer cell activity induced by laughter in a crossover designed study. Int J Mol Med. 2001;8:645-650.
21. Nasir UM, Iwanaga S, Nabi AH, et al. Laughter therapy modulates the parameters of renin-angiotensin system in patients with type 2 diabetes. Int J Mol Med. 2005;16:1077-1081.
22. Clark A, Seidler A, Miller M. Inverse association between sense of humor and coronary heart disease. Int J Cardiol. 2001;80:87-88.
23. Cousins N. The anatomy of an illness as perceived by the patient: reflections on healing and regeneration. New York, NY: Norton; 1979:39.
24. Dunbar RI, Baron R, Frangou A, et al. Social laughter is correlated with an elevated pain threshold. Proc Biol Sci. 2012;279(1731):1161-1167.
25. Ko HJ, Youn CH. Effects of laughter therapy on depression, cognition and sleep among the community-dwelling elderly. Geriatr Gerontol Int. 2011;11:267-274.
26. Shahidi M, Mojtahed A, Modabbernia A, et al. Laughter yoga versus group exercise program in elderly depressed women: a randomized controlled trial. Int J Geriatr Psychiatry. 2011;26:322-327.
27. Fonzi L, Matteucci G, Bersani G. Laughter and depression: hypothesis of pathogenic and therapeutic correlation. Riv Psichiatr. 2010;45:1-6.
28. Levinson W, Roter DL, Mullooly JP, et al. Physician-patient communication: the relationship with malpractice claims among primary care physicians and surgeons. JAMA. 1997;277:553-559.
29. Lebowitz KR, Suh S, Diaz PT, et al. Effects of humor and laughter on psychological functioning, quality of life, health status, and pulmonary functioning among patients with chronic obstructive pulmonary disease: a preliminary investigation. Heart Lung. 2011;40:310-319.
CASE REPORT: Laughter as therapy
Mrs. A is a 56-year-old married woman who has bipolar disorder. She has survived several suicide attempts. Her family history is positive for bipolar disorder and completed suicides.
After her most recent suicide attempt and a course of electroconvulsive therapy, Mrs. A recovered sufficiently to begin a spiritual journey that led her to practice a technique known as Laughter Yoga (Box) and, eventually, to become a Laughter Yoga instructor.
Mrs. A begins Laughter Yoga sessions by talking openly with students about her illness and the beneficial effects that laughter therapy has had on its course: She once had at least two major bipolar episodes a year, she explains, but has been in full remission for several years despite severe psychosocial stressors. In addition to practicing Laughter Yoga, Mrs. A is now maintained on a mood stabilizer that failed in the past to control her mood cycles.
Does laughter have a place in your practice?
It is said that laughter is good medicine—but is it good psychiatric medicine? Where might humor and laughter fit in the psychiatrist’s armamentarium? Is laughter physiologically beneficial to psychiatric patients? And are there adverse effects or contraindications to laughter in psychiatry? This article:
• reviews studies that have examined the anatomy, physiology, and psychology of humor and laughtera
• offers answers to the questions posed above (Table).
“Gelotology,” from the Greek “gelos,” laughter, is the science of laughter. The three components of humor and laughter are:
• the emotional component, which triggers emotions produced by a humorous situation
• the cognitive component, in which a person “gets it”
• the movement of facial, respiratory, and abdominal muscles.
Furthermore, tension and surprise are needed for laughter.
Theories about humor are varied
Philosophers since Plato have proposed theories of humor; modern theories of humor can be traced to Freud’s work.1 The psychoanalytic literature on humor focuses on the role of humor in sublimation of feelings of anger and hostility, while releasing affect in an economical way.
Erikson also wrote about the role of humor in a child’s developing superego, which helps resolve the conflict with maternal authority.2
In a comprehensive review of theories of humor, Krichtafovitch explains that cognitive theories address the role of incongruity and contrast in the induction of laughter, whereas social theories explore the roles of aggression, hostility, superiority, triumph, derision, and disparagement in humor and laughter. The effect of humor, Krichtafovitch explains, is to elevate the social status of the joker while the listener’s social status is lifted through his (her) ability to “get it.” Thus, humor plays a meaningful role in creating a bond between speaker and listener.3
The neuroanatomy of laughter
Here is some of what we have learned about mapping the brain to the basis of laughter:
• Consider a 16-year-old girl who underwent neurosurgery for intractable seizures. During surgery, various parts of the brain were stimulated to test for the focus of the seizures. She laughed every time the left frontal superior gyrus was stimulated. According to the report, she apparently laughed first, then made up a story that was funny to her.4
• Pseudobulbar affect—excessive, usually incongruent laughter, secondary to neurologic disease or traumatic brain injury—is an example of the biologic basis of laughter.
• Many functional brain imaging studies of laughter have been published.5 These studies show involvement of various regions of the brain in laughter, including the amygdala, hypothalamus, and temporal and cerebellar regions.
• Sex differences also have been noted in the neuroanatomy of laughter. Females activate the left prefrontal cortex more than males do, suggesting a greater degree of executive processing and language-based decoding. Females also exhibit greater activation of mesolimbic regions, including the nucleus accumbens, implying a greater reward network response.6
• Wild et al7 reported that separate cortical regions are responsible for the production of facial expressions that are emotionally driven (through laughter) and voluntary.
The physiology of laughter
Humans begin to laugh at approximately 4 months of age. Children laugh, on average, 400 times a day; adults do so an average of only 5 times a day.8 In addition:
• Tickling a baby induces her (him) to laugh, which, in turn, makes the parent laugh; a social bond develops during this playful exercise. This response is probably mediated by 5-HT1A receptors, which, when stimulated, induces the release of oxytocin, which facilitates social bonding.9
• Potent stimulation of 5-HT1A receptors through ingestion of 3,4-methylenedioxy-N-methylamphetamine (Ecstasy) leads to uncontrollable laughter and mirth.10
• Lower species are also known to enjoy humor. Mice emit a chirping sound when tickled, and laughter is contagious among monkeys.11
• Berk et al12,13 reported that, when 52 healthy men watched a funny video for 30 minutes, they had significantly higher activity of natural killer (NK) cells and higher levels of IgG, IgA, and IgM compared with men who watched an emotionally neutral documentary.
• Bennett et al14 showed that, in 33 healthy women, the harder the laughter, the higher the NK activity.
• Sugawara et al15 showed improved cardiovascular function in 17 healthy persons (age 23 to 42) who watched a 30-minute comedy video, compared with their cardiovascular function when they watched a documentary video of equal length.
• Svebak et al16 examined the effect of humor as measured by the Sense of Humor Survey on the survival rate of more then 53,000 adults in one county in Norway. They concluded that the higher the sense of humor score, the higher the odds ratio of surviving 7 years, compared with subjects who had a lower sense of humor.
Clinical studies of laughter
The Coping Humor Scale (CHS) and the Humor Response Scale (HRS) are the two most widely used tools to measure a person’s innate sense of humor (the CHS) and the ability to respond to a humorous situation (the HRS).17 Several studies about the effects of laughter on illness are notable:
• Laughter increased NK cell activity, lowered prorenin gene expression, and lowered the postprandial glucose level in 34 patients with diabetes, compared with 16 matched controls.18-21
• Clark et al studied the sense of humor of 150 patients with cardiac disease compared with 150 controls. They found that “people with heart disease responded less humorously to everyday life situations.” They generally laughed less, even in positive situations, and displayed more anger and hostility.22
• In his work on the salutatory effect of laughter on the experience of pain, Cousins described how he dealt with his painful arthritis by watching Marx Brothers movies23:
I made the joyous discovery that 10 minutes of genuine belly laughter had an anesthetic effect and would give me at least two hours of pain-free sleep… When the pain-killing effect of the laughter wore off, we would switch on the motion picture projector again and not infrequently, it would lead to another pain-free interval.
• Hearty laughter leads to pain relief, probably through the release of endorphins. Dunbar et al24 tested this hypothesis in a series of six experimental studies in the laboratory (watching videos) and in a naturalistic context (watching stage performances), using a change in pain threshold as an indirect measure of endorphin release. The results show that the pain threshold is significantly higher after laughter than in the control condition. This pain-tolerance effect is caused by the laughter itself, not simply because of a change in positive affect.
Laughter therapy for depression
Three studies have demonstrated the benefit of laughter therapy in depression:
• When Ko and Youn25 studied 48 geriatric depressed patients and 61 age-matched controls, they found a significantly lower Geriatric Depression Scale score and a better Pittsburgh Sleep Quality Index score in patients who had been exposed to four weekly laughter groups, compared with persons who had been exposed to a control group.
• Shahidi et al26 randomly assigned 60 community-dwelling female, geriatric, depressed patients to a laughter yoga group, an exercise group, and a control group. Laughter yoga and exercise were equally effective, and both were significantly superior to the control condition. The laughter yoga group scored significantly better than the other two groups on the Life Satisfaction Scale. The researchers concluded that, in addition to improved mood, patients who laugh experience increased life satisfaction.
• Fonzi et al27 summarized data on the neurophysiology of laughter and the effect of laughter on the hypothalamus-pituitary-adrenal axis. They noted that depression reduces the frequency of laughter and, inversely, laughter reduces the severity of depression. Laughter, they reported, also increases the connectivity of patients with people in their life, which further alleviates symptoms of depression.
Other therapeutic uses of laughter
Humor can strengthen the bond of the therapeutic relationship. Patients who laugh with their physicians are more likely to feel connected with them, follow their advice, and feel more satisfied with their encounter. One study found that primary care physicians who gave positive statements, spent more time with patients, and included humor or laughter during their visits lowered their risk of being sued for malpractice.28
Consider also the use of laughter in altering family dynamics in a therapeutic setting: Mr. and Mrs. B attend therapy in my practice to address a difficult situation with their adult children. One of them enables their children socially and financially; the other continually complains about this enabling. When the tension was high and the couple had reached an impasse during a visit, the therapist offered an anecdote from the 2006 motion picture Failure to Launch (in which a man lives in the security of his parents’ home even though he is in his 30s), that dissipated the hostility they had shown toward each other and toward their children. The couple was then able to proceed to conflict resolution.
Recommendations, caveats
If you are considering incorporating laughter into therapy, keep in mind that:
• you should ensure that the patient does not perceive humor as minimizing the seriousness of their problems
• humor can be a minefield if not used judiciously, or if used at all, around certain sensitive topics, such as race, ethnicity, religion, political affiliation, and sexual orientation
• the timing of humor is particularly essential for it to succeed in the context of a therapeutic relationship
• from a medical perspective, laughter in patients who are recovering from abdominal or other major surgery might compromise wound healing because of increased intra-abdominal pressure associated with laughing
• patients who have asthma, especially exercise-induced asthma, might be at risk of developing an acute asthmatic attack when they laugh very hard. Lebowitz et al29 demonstrated that laughter can have a negative effect on patients with chronic obstructive pulmonary disease.
It is advisable in some situations to avoid humor in psychotherapy, such as when the patient or family is hostile—because, as noted, they might perceive laughter and humor as an attempt to minimize the seriousness of their discontent.
Bottom Line
Humor and laughter are underutilized and underreported in therapy, in part because it is a nascent field of research. Laughter has social and physiologic benefits that can be used in the context of a therapeutic relationship to help patients with a variety of ailments, including depression, anxiety, and pain.
Related Resources
- Association for Applied and Therapeutic Humor. www.aath.org.
- Mora-Ripoll R. The therapeutic value of laughter in medicine. Altern Ther Health Med. 2010;16:56-64.
- Strean WB. Laughter prescription. Can Fam Physician. 2009;55:965-967.
Disclosure
Dr. Nasr reports no financial relationship with manufacturers of any products mentioned in this article or with manufacturers of competing products.
Acknowledgements
The author acknowledges the assistance of Francois E. Alouf, MD, for suggestions on topics to include in the article; John W. Crayton, MD, for reviewing the manuscript; and Burdette Wendt for assistance with the references.
CASE REPORT: Laughter as therapy
Mrs. A is a 56-year-old married woman who has bipolar disorder. She has survived several suicide attempts. Her family history is positive for bipolar disorder and completed suicides.
After her most recent suicide attempt and a course of electroconvulsive therapy, Mrs. A recovered sufficiently to begin a spiritual journey that led her to practice a technique known as Laughter Yoga (Box) and, eventually, to become a Laughter Yoga instructor.
Mrs. A begins Laughter Yoga sessions by talking openly with students about her illness and the beneficial effects that laughter therapy has had on its course: She once had at least two major bipolar episodes a year, she explains, but has been in full remission for several years despite severe psychosocial stressors. In addition to practicing Laughter Yoga, Mrs. A is now maintained on a mood stabilizer that failed in the past to control her mood cycles.
Does laughter have a place in your practice?
It is said that laughter is good medicine—but is it good psychiatric medicine? Where might humor and laughter fit in the psychiatrist’s armamentarium? Is laughter physiologically beneficial to psychiatric patients? And are there adverse effects or contraindications to laughter in psychiatry? This article:
• reviews studies that have examined the anatomy, physiology, and psychology of humor and laughtera
• offers answers to the questions posed above (Table).
“Gelotology,” from the Greek “gelos,” laughter, is the science of laughter. The three components of humor and laughter are:
• the emotional component, which triggers emotions produced by a humorous situation
• the cognitive component, in which a person “gets it”
• the movement of facial, respiratory, and abdominal muscles.
Furthermore, tension and surprise are needed for laughter.
Theories about humor are varied
Philosophers since Plato have proposed theories of humor; modern theories of humor can be traced to Freud’s work.1 The psychoanalytic literature on humor focuses on the role of humor in sublimation of feelings of anger and hostility, while releasing affect in an economical way.
Erikson also wrote about the role of humor in a child’s developing superego, which helps resolve the conflict with maternal authority.2
In a comprehensive review of theories of humor, Krichtafovitch explains that cognitive theories address the role of incongruity and contrast in the induction of laughter, whereas social theories explore the roles of aggression, hostility, superiority, triumph, derision, and disparagement in humor and laughter. The effect of humor, Krichtafovitch explains, is to elevate the social status of the joker while the listener’s social status is lifted through his (her) ability to “get it.” Thus, humor plays a meaningful role in creating a bond between speaker and listener.3
The neuroanatomy of laughter
Here is some of what we have learned about mapping the brain to the basis of laughter:
• Consider a 16-year-old girl who underwent neurosurgery for intractable seizures. During surgery, various parts of the brain were stimulated to test for the focus of the seizures. She laughed every time the left frontal superior gyrus was stimulated. According to the report, she apparently laughed first, then made up a story that was funny to her.4
• Pseudobulbar affect—excessive, usually incongruent laughter, secondary to neurologic disease or traumatic brain injury—is an example of the biologic basis of laughter.
• Many functional brain imaging studies of laughter have been published.5 These studies show involvement of various regions of the brain in laughter, including the amygdala, hypothalamus, and temporal and cerebellar regions.
• Sex differences also have been noted in the neuroanatomy of laughter. Females activate the left prefrontal cortex more than males do, suggesting a greater degree of executive processing and language-based decoding. Females also exhibit greater activation of mesolimbic regions, including the nucleus accumbens, implying a greater reward network response.6
• Wild et al7 reported that separate cortical regions are responsible for the production of facial expressions that are emotionally driven (through laughter) and voluntary.
The physiology of laughter
Humans begin to laugh at approximately 4 months of age. Children laugh, on average, 400 times a day; adults do so an average of only 5 times a day.8 In addition:
• Tickling a baby induces her (him) to laugh, which, in turn, makes the parent laugh; a social bond develops during this playful exercise. This response is probably mediated by 5-HT1A receptors, which, when stimulated, induces the release of oxytocin, which facilitates social bonding.9
• Potent stimulation of 5-HT1A receptors through ingestion of 3,4-methylenedioxy-N-methylamphetamine (Ecstasy) leads to uncontrollable laughter and mirth.10
• Lower species are also known to enjoy humor. Mice emit a chirping sound when tickled, and laughter is contagious among monkeys.11
• Berk et al12,13 reported that, when 52 healthy men watched a funny video for 30 minutes, they had significantly higher activity of natural killer (NK) cells and higher levels of IgG, IgA, and IgM compared with men who watched an emotionally neutral documentary.
• Bennett et al14 showed that, in 33 healthy women, the harder the laughter, the higher the NK activity.
• Sugawara et al15 showed improved cardiovascular function in 17 healthy persons (age 23 to 42) who watched a 30-minute comedy video, compared with their cardiovascular function when they watched a documentary video of equal length.
• Svebak et al16 examined the effect of humor as measured by the Sense of Humor Survey on the survival rate of more then 53,000 adults in one county in Norway. They concluded that the higher the sense of humor score, the higher the odds ratio of surviving 7 years, compared with subjects who had a lower sense of humor.
Clinical studies of laughter
The Coping Humor Scale (CHS) and the Humor Response Scale (HRS) are the two most widely used tools to measure a person’s innate sense of humor (the CHS) and the ability to respond to a humorous situation (the HRS).17 Several studies about the effects of laughter on illness are notable:
• Laughter increased NK cell activity, lowered prorenin gene expression, and lowered the postprandial glucose level in 34 patients with diabetes, compared with 16 matched controls.18-21
• Clark et al studied the sense of humor of 150 patients with cardiac disease compared with 150 controls. They found that “people with heart disease responded less humorously to everyday life situations.” They generally laughed less, even in positive situations, and displayed more anger and hostility.22
• In his work on the salutatory effect of laughter on the experience of pain, Cousins described how he dealt with his painful arthritis by watching Marx Brothers movies23:
I made the joyous discovery that 10 minutes of genuine belly laughter had an anesthetic effect and would give me at least two hours of pain-free sleep… When the pain-killing effect of the laughter wore off, we would switch on the motion picture projector again and not infrequently, it would lead to another pain-free interval.
• Hearty laughter leads to pain relief, probably through the release of endorphins. Dunbar et al24 tested this hypothesis in a series of six experimental studies in the laboratory (watching videos) and in a naturalistic context (watching stage performances), using a change in pain threshold as an indirect measure of endorphin release. The results show that the pain threshold is significantly higher after laughter than in the control condition. This pain-tolerance effect is caused by the laughter itself, not simply because of a change in positive affect.
Laughter therapy for depression
Three studies have demonstrated the benefit of laughter therapy in depression:
• When Ko and Youn25 studied 48 geriatric depressed patients and 61 age-matched controls, they found a significantly lower Geriatric Depression Scale score and a better Pittsburgh Sleep Quality Index score in patients who had been exposed to four weekly laughter groups, compared with persons who had been exposed to a control group.
• Shahidi et al26 randomly assigned 60 community-dwelling female, geriatric, depressed patients to a laughter yoga group, an exercise group, and a control group. Laughter yoga and exercise were equally effective, and both were significantly superior to the control condition. The laughter yoga group scored significantly better than the other two groups on the Life Satisfaction Scale. The researchers concluded that, in addition to improved mood, patients who laugh experience increased life satisfaction.
• Fonzi et al27 summarized data on the neurophysiology of laughter and the effect of laughter on the hypothalamus-pituitary-adrenal axis. They noted that depression reduces the frequency of laughter and, inversely, laughter reduces the severity of depression. Laughter, they reported, also increases the connectivity of patients with people in their life, which further alleviates symptoms of depression.
Other therapeutic uses of laughter
Humor can strengthen the bond of the therapeutic relationship. Patients who laugh with their physicians are more likely to feel connected with them, follow their advice, and feel more satisfied with their encounter. One study found that primary care physicians who gave positive statements, spent more time with patients, and included humor or laughter during their visits lowered their risk of being sued for malpractice.28
Consider also the use of laughter in altering family dynamics in a therapeutic setting: Mr. and Mrs. B attend therapy in my practice to address a difficult situation with their adult children. One of them enables their children socially and financially; the other continually complains about this enabling. When the tension was high and the couple had reached an impasse during a visit, the therapist offered an anecdote from the 2006 motion picture Failure to Launch (in which a man lives in the security of his parents’ home even though he is in his 30s), that dissipated the hostility they had shown toward each other and toward their children. The couple was then able to proceed to conflict resolution.
Recommendations, caveats
If you are considering incorporating laughter into therapy, keep in mind that:
• you should ensure that the patient does not perceive humor as minimizing the seriousness of their problems
• humor can be a minefield if not used judiciously, or if used at all, around certain sensitive topics, such as race, ethnicity, religion, political affiliation, and sexual orientation
• the timing of humor is particularly essential for it to succeed in the context of a therapeutic relationship
• from a medical perspective, laughter in patients who are recovering from abdominal or other major surgery might compromise wound healing because of increased intra-abdominal pressure associated with laughing
• patients who have asthma, especially exercise-induced asthma, might be at risk of developing an acute asthmatic attack when they laugh very hard. Lebowitz et al29 demonstrated that laughter can have a negative effect on patients with chronic obstructive pulmonary disease.
It is advisable in some situations to avoid humor in psychotherapy, such as when the patient or family is hostile—because, as noted, they might perceive laughter and humor as an attempt to minimize the seriousness of their discontent.
Bottom Line
Humor and laughter are underutilized and underreported in therapy, in part because it is a nascent field of research. Laughter has social and physiologic benefits that can be used in the context of a therapeutic relationship to help patients with a variety of ailments, including depression, anxiety, and pain.
Related Resources
- Association for Applied and Therapeutic Humor. www.aath.org.
- Mora-Ripoll R. The therapeutic value of laughter in medicine. Altern Ther Health Med. 2010;16:56-64.
- Strean WB. Laughter prescription. Can Fam Physician. 2009;55:965-967.
Disclosure
Dr. Nasr reports no financial relationship with manufacturers of any products mentioned in this article or with manufacturers of competing products.
Acknowledgements
The author acknowledges the assistance of Francois E. Alouf, MD, for suggestions on topics to include in the article; John W. Crayton, MD, for reviewing the manuscript; and Burdette Wendt for assistance with the references.
1. Freud S, Strachey J, trans., ed. Jokes and their relation to the unconscious. New York, NY: W. W. Norton & Company; 1990.
2. Capps D. Mother, melancholia, and humor in Erik H. Erikson’s earliest writings. J Relig Health. 2008;47:415-432.
3. Krichtafovitch I. Humor theory. Parker, CO: Outskirts Press; 2006.
4. Fried I, Wilson CL, MacDonald KA, et al. Electric current stimulates laughter. Nature. 1998;12;391:650.
5. Bartolo A, Benuzzi F, Nocetti L, et al. Humor comprehension and appreciation: an FMRI study. J Cogn Neurosci. 2006;18:1789-1798.
6. Azim E, Mobbs D, Jo B, et al. Sex differences in brain activation elicited by humor. Proc Natl Acad Sci U S A. 2005;102:16496-16501.
7. Wild B, Rodden FA, Rapp A, et al. Humor and smiling: cortical regions selective for cognitive, affective, and volitional components. Neurology. 2006;66:887-893.
8. Freedman LW. Mosby’s complementary and alternative medicine. A research-based approach. St. Louis, MO: Mosby; 2004:24.
9. Lukas M, Toth I, Reber SO, et al. The neuropeptide oxytocin facilitates pro-social behavior and prevents social avoidance in rats and mice. Neuropsychopharmacology. 2011;36:
2159-2168.
10. Thompson MR, Callaghan PD, Hunt GE, et al. A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine (“ecstasy”). Neuroscience. 2007;146:509-514.
11. Ross MD, Owren MJ, Zimmermann E. The evolution of laughter in great apes and humans. Commun Integr Biol. 2010;3(2):191-194.
12. Berk LS, Tan SA, Fry WF, et al. Neuroendocrine and stress hormone changes during mirthful laughter. Am J Med Sci. 1989;298:390-396.
13. Berk LS, Felten DL, Tan SA, et al. Modulation of neuroimmune parameters during the eustress of humor-associated mirthful laughter. Altern Ther Health Med. 2001; 7:62-72,74-76.
14. Bennett MP, Zeller JM, Rosenberg L, et al. The effect of mirthful laughter on stress and natural killer cell activity. Altern Ther Health Med. 2003;9:38-45.
15. Sugawara J, Tarumi T, Tanaka H. Effect of mirthful laughter on vascular function. Am J Cardiol. 2010;106:856-859.
16. Svebak S, Romundstad S, Holmen J. A 7-year prospective study of sense of humor and mortality in an adult county population: the HUNT-2 study. Int J Psychiatry Med. 2010;40:125-146.
17. Martin RA. The Situational Humor Response Questionnaire (SHRQ) and Coping Humor Scale (CHS): a decade of research findings. Humor: International Journal of Humor Research. 1996;9(3-4):251-272.
18. Hayashi T, Urayama O, Hori M, et al. Laughter modulates prorenin receptor gene expression in patients with type 2 diabetes. J Psychosom Res. 2007;62:703-706.
19. Hayashi T, Murakami K. The effects of laughter on post-prandial glucose levels and gene expression in type 2 diabetic patients. Life Sci. 2009;85:185-187.
20. Takahashi K, Iwase M, Yamashita K, et al. The elevation of natural killer cell activity induced by laughter in a crossover designed study. Int J Mol Med. 2001;8:645-650.
21. Nasir UM, Iwanaga S, Nabi AH, et al. Laughter therapy modulates the parameters of renin-angiotensin system in patients with type 2 diabetes. Int J Mol Med. 2005;16:1077-1081.
22. Clark A, Seidler A, Miller M. Inverse association between sense of humor and coronary heart disease. Int J Cardiol. 2001;80:87-88.
23. Cousins N. The anatomy of an illness as perceived by the patient: reflections on healing and regeneration. New York, NY: Norton; 1979:39.
24. Dunbar RI, Baron R, Frangou A, et al. Social laughter is correlated with an elevated pain threshold. Proc Biol Sci. 2012;279(1731):1161-1167.
25. Ko HJ, Youn CH. Effects of laughter therapy on depression, cognition and sleep among the community-dwelling elderly. Geriatr Gerontol Int. 2011;11:267-274.
26. Shahidi M, Mojtahed A, Modabbernia A, et al. Laughter yoga versus group exercise program in elderly depressed women: a randomized controlled trial. Int J Geriatr Psychiatry. 2011;26:322-327.
27. Fonzi L, Matteucci G, Bersani G. Laughter and depression: hypothesis of pathogenic and therapeutic correlation. Riv Psichiatr. 2010;45:1-6.
28. Levinson W, Roter DL, Mullooly JP, et al. Physician-patient communication: the relationship with malpractice claims among primary care physicians and surgeons. JAMA. 1997;277:553-559.
29. Lebowitz KR, Suh S, Diaz PT, et al. Effects of humor and laughter on psychological functioning, quality of life, health status, and pulmonary functioning among patients with chronic obstructive pulmonary disease: a preliminary investigation. Heart Lung. 2011;40:310-319.
1. Freud S, Strachey J, trans., ed. Jokes and their relation to the unconscious. New York, NY: W. W. Norton & Company; 1990.
2. Capps D. Mother, melancholia, and humor in Erik H. Erikson’s earliest writings. J Relig Health. 2008;47:415-432.
3. Krichtafovitch I. Humor theory. Parker, CO: Outskirts Press; 2006.
4. Fried I, Wilson CL, MacDonald KA, et al. Electric current stimulates laughter. Nature. 1998;12;391:650.
5. Bartolo A, Benuzzi F, Nocetti L, et al. Humor comprehension and appreciation: an FMRI study. J Cogn Neurosci. 2006;18:1789-1798.
6. Azim E, Mobbs D, Jo B, et al. Sex differences in brain activation elicited by humor. Proc Natl Acad Sci U S A. 2005;102:16496-16501.
7. Wild B, Rodden FA, Rapp A, et al. Humor and smiling: cortical regions selective for cognitive, affective, and volitional components. Neurology. 2006;66:887-893.
8. Freedman LW. Mosby’s complementary and alternative medicine. A research-based approach. St. Louis, MO: Mosby; 2004:24.
9. Lukas M, Toth I, Reber SO, et al. The neuropeptide oxytocin facilitates pro-social behavior and prevents social avoidance in rats and mice. Neuropsychopharmacology. 2011;36:
2159-2168.
10. Thompson MR, Callaghan PD, Hunt GE, et al. A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine (“ecstasy”). Neuroscience. 2007;146:509-514.
11. Ross MD, Owren MJ, Zimmermann E. The evolution of laughter in great apes and humans. Commun Integr Biol. 2010;3(2):191-194.
12. Berk LS, Tan SA, Fry WF, et al. Neuroendocrine and stress hormone changes during mirthful laughter. Am J Med Sci. 1989;298:390-396.
13. Berk LS, Felten DL, Tan SA, et al. Modulation of neuroimmune parameters during the eustress of humor-associated mirthful laughter. Altern Ther Health Med. 2001; 7:62-72,74-76.
14. Bennett MP, Zeller JM, Rosenberg L, et al. The effect of mirthful laughter on stress and natural killer cell activity. Altern Ther Health Med. 2003;9:38-45.
15. Sugawara J, Tarumi T, Tanaka H. Effect of mirthful laughter on vascular function. Am J Cardiol. 2010;106:856-859.
16. Svebak S, Romundstad S, Holmen J. A 7-year prospective study of sense of humor and mortality in an adult county population: the HUNT-2 study. Int J Psychiatry Med. 2010;40:125-146.
17. Martin RA. The Situational Humor Response Questionnaire (SHRQ) and Coping Humor Scale (CHS): a decade of research findings. Humor: International Journal of Humor Research. 1996;9(3-4):251-272.
18. Hayashi T, Urayama O, Hori M, et al. Laughter modulates prorenin receptor gene expression in patients with type 2 diabetes. J Psychosom Res. 2007;62:703-706.
19. Hayashi T, Murakami K. The effects of laughter on post-prandial glucose levels and gene expression in type 2 diabetic patients. Life Sci. 2009;85:185-187.
20. Takahashi K, Iwase M, Yamashita K, et al. The elevation of natural killer cell activity induced by laughter in a crossover designed study. Int J Mol Med. 2001;8:645-650.
21. Nasir UM, Iwanaga S, Nabi AH, et al. Laughter therapy modulates the parameters of renin-angiotensin system in patients with type 2 diabetes. Int J Mol Med. 2005;16:1077-1081.
22. Clark A, Seidler A, Miller M. Inverse association between sense of humor and coronary heart disease. Int J Cardiol. 2001;80:87-88.
23. Cousins N. The anatomy of an illness as perceived by the patient: reflections on healing and regeneration. New York, NY: Norton; 1979:39.
24. Dunbar RI, Baron R, Frangou A, et al. Social laughter is correlated with an elevated pain threshold. Proc Biol Sci. 2012;279(1731):1161-1167.
25. Ko HJ, Youn CH. Effects of laughter therapy on depression, cognition and sleep among the community-dwelling elderly. Geriatr Gerontol Int. 2011;11:267-274.
26. Shahidi M, Mojtahed A, Modabbernia A, et al. Laughter yoga versus group exercise program in elderly depressed women: a randomized controlled trial. Int J Geriatr Psychiatry. 2011;26:322-327.
27. Fonzi L, Matteucci G, Bersani G. Laughter and depression: hypothesis of pathogenic and therapeutic correlation. Riv Psichiatr. 2010;45:1-6.
28. Levinson W, Roter DL, Mullooly JP, et al. Physician-patient communication: the relationship with malpractice claims among primary care physicians and surgeons. JAMA. 1997;277:553-559.
29. Lebowitz KR, Suh S, Diaz PT, et al. Effects of humor and laughter on psychological functioning, quality of life, health status, and pulmonary functioning among patients with chronic obstructive pulmonary disease: a preliminary investigation. Heart Lung. 2011;40:310-319.
