Tolerability and Safety of Transcranial Photobiomodulation for Mood and Anxiety Disorders
Abstract
:1. Introduction
1.1. Conventional Treatments for Major Depressive Disorder
1.2. Conventional Treatments for Generalized Anxiety Disorder
1.3. Non-Pharmacological Interventions for Mood and Anxiety Disorders
1.4. Transcranial Photobiomodulation
1.5. Tolerability and Safety of Transcranial Photobiomodulation
2. Materials and Methods
2.1. Inclusion and Exclusion Criteria
2.2. Sample
2.3. Procedures
2.4. Outcome Measures
2.5. Statistical Analyses
3. Results
3.1. Sample
3.2. NIR vs. Sham Group Comparison
3.3. Within NIR Group Comparison
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Kessler, R.C.; Berglund, P.; Demler, O.; Jin, R.; Koretz, D.; Merikangas, K.R.; Rush, A.J.; Walters, E.E.; Wang, P.S. The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003, 289, 3095–3105. [Google Scholar] [CrossRef]
- Ferrari, A.J.; Charlson, F.J.; Norman, R.E.; Patten, S.B.; Freedman, G.; Murray, C.J.; Vos, T.; Whiteford, H.A. Burden of depressive disorders by country, sex, age, and year: Findings from the global burden of disease study 2010. PLoS Med. 2013, 10, e1001547. [Google Scholar] [CrossRef] [Green Version]
- Cassano, P.; Fava, M. Tolerability issues during long-term treatment with antidepressants. Ann. Clin. Psychiatry 2004, 16, 15–25. [Google Scholar] [CrossRef]
- Kennedy, S.H.; Lam, R.W.; McIntyre, R.S.; Tourjman, S.V.; Bhat, V.; Blier, P.; Hasnain, M.; Jollant, F.; Levitt, A.J.; MacQueen, G.M.; et al. Canadian network for mood and anxiety treatments (CANMAT) 2016 clinical guidelines for the management of adults with major depressive disorder: Section 3. Pharmacological treatments. Can. J. Psychiatry 2016, 61, 540–560. [Google Scholar] [CrossRef]
- Rush, A.J.; Warden, D.; Wisniewski, S.R.; Fava, M.; Trivedi, M.H.; Gaynes, B.N.; Nierenberg, A.A. STAR*D: Revising conventional wisdom. CNS Drugs 2009, 23, 627–647. [Google Scholar]
- Sinyor, M.; Schaffer, A.; Levitt, A. The sequenced treatment alternatives to relieve depression (STAR*D) trial: A review. Can. J. Psychiatry 2010, 55, 126–135. [Google Scholar] [CrossRef] [Green Version]
- Ferguson, J.M. SSRI antidepressant medications: Adverse effects and tolerability. Prim. Care Companion J. Clin. Psychiatry 2001, 3, 22–27. [Google Scholar] [CrossRef]
- Bystritsky, A.; Khalsa, S.S.; Cameron, M.E.; Schiffman, J. Current diagnosis and treatment of anxiety disorders. Pharm. Ther. 2013, 38, 30–57. [Google Scholar]
- Ruscio, A.M.; Hallion, L.S.; Lim, C.C.W.; Aguilar-Gaxiola, S.; Al-Hamzawi, A.; Alonso, J.; Andrade, L.H.; Borges, G.; Bromet, E.J.; Bunting, B.; et al. Cross-sectional comparison of the epidemiology of DSM-5 generalized anxiety disorder across the globe. JAMA Psychiatry 2017, 74, 465–475. [Google Scholar] [CrossRef] [Green Version]
- Davidson, J.R. First-line pharmacotherapy approaches for generalized anxiety disorder. J. Clin. Psychiatry 2009, 70 (Suppl. 2), 25–31. [Google Scholar] [CrossRef] [Green Version]
- Cvjetkovic-Bosnjak, M.; Soldatovic-Stajic, B.; Babovic, S.S.; Boskovic, K.; Jovicevic, M. Pregabalin versus sertraline in generalized anxiety disorder. An open label study. Eur. Rev. Med. Pharmacol. Sci. 2015, 19, 2120–2124. [Google Scholar]
- Baldwin, D.S.; Waldman, S.; Allgulander, C. Evidence-based pharmacological treatment of generalized anxiety disorder. Int. J. Neuropsychopharmacol. 2011, 14, 697–710. [Google Scholar] [CrossRef]
- Burstein, O.; Shamir, A.; Abramovitz, N.; Doron, R. Patients’ attitudes toward conventional and herbal treatments for depression and anxiety: A cross-sectional Israeli survey. Int. J. Soc. Psychiatry 2022, 68, 589–599. [Google Scholar] [CrossRef]
- Cassano, P.; Petrie, S.R.; Hamblin, M.R.; Henderson, T.A.; Iosifescu, D.V. Review of transcranial photobiomodulation for major depressive disorder: Targeting brain metabolism, inflammation, oxidative stress, and neurogenesis. Neurophotonics 2016, 3, 031404. [Google Scholar] [CrossRef] [Green Version]
- Salehpour, F.; Mahmoudi, J.; Kamari, F.; Sadigh-Eteghad, S.; Rasta, S.H.; Hamblin, M.R. Brain photobiomodulation therapy: A narrative review. Mol. Neurobiol. 2018, 55, 6601–6636. [Google Scholar] [CrossRef]
- Cassano, P.; Cusin, C.; Mischoulon, D.; Hamblin, M.R.; De Taboada, L.; Pisoni, A.; Chang, T.; Yeung, A.; Ionescu, D.F.; Petrie, S.R.; et al. Near-infrared transcranial radiation for major depressive disorder: Proof of concept study. Psychiatry J. 2015, 2015, 352979. [Google Scholar] [CrossRef]
- Schiffer, F.; Johnston, A.L.; Ravichandran, C.; Polcari, A.; Teicher, M.H.; Webb, R.H.; Hamblin, M.R. Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: A pilot study of 10 patients with major depression and anxiety. Behav. Brain Funct. 2009, 5, 46. [Google Scholar] [CrossRef] [Green Version]
- Karu, T.I. Molecular mechanism of the therapeutic effect of low-intensity laser irradiation. Dokl. Akad. Nauk SSSR 1986, 291, 1245–1249. [Google Scholar]
- Mochizuki-Oda, N.; Kataoka, Y.; Cui, Y.; Yamada, H.; Heya, M.; Awazu, K. Effects of near-infra-red laser irradiation on adenosine triphosphate and adenosine diphosphate contents of rat brain tissue. Neurosci. Lett. 2002, 323, 207–210. [Google Scholar] [CrossRef]
- Oron, U.; Ilic, S.; De Taboada, L.; Streeter, J. Ga-As (808 nm) laser irradiation enhances ATP production in human neuronal cells in culture. Photomed. Laser Surg. 2007, 25, 180–182. [Google Scholar] [CrossRef]
- Nagafusa, Y.; Okamoto, N.; Sakamoto, K.; Yamashita, F.; Kawaguchi, A.; Higuchi, T.; Matsuda, H. Assessment of cerebral blood flow findings using 99mTc-ECD single-photon emission computed tomography in patients diagnosed with major depressive disorder. J. Affect. Disord. 2012, 140, 296–299. [Google Scholar] [CrossRef]
- Caldieraro, M.A.; Cassano, P. Transcranial and systemic photobiomodulation for major depressive disorder: A systematic review of efficacy, tolerability and biological mechanisms. J. Affect. Disord. 2019, 243, 262–273. [Google Scholar] [CrossRef]
- Cassano, P.; Petrie, S.R.; Mischoulon, D.; Cusin, C.; Katnani, H.; Yeung, A.; De Taboada, L.; Archibald, A.; Bui, E.; Baer, L.; et al. Transcranial photobiomodulation for the treatment of major depressive disorder. The ELATED-2 pilot trial. Photomed. Laser Surg. 2018, 36, 634–646. [Google Scholar] [CrossRef] [Green Version]
- Lampl, Y.; Zivin, J.A.; Fisher, M.; Lew, R.; Welin, L.; Dahlof, B.; Borenstein, P.; Andersson, B.; Perez, J.; Caparo, C.; et al. Infrared laser therapy for ischemic stroke: A new treatment strategy: Results of the NeuroThera effectiveness and safety trial-1 (NEST-1). Stroke 2007, 38, 1843–1849. [Google Scholar] [CrossRef] [Green Version]
- Huisa, B.N.; Stemer, A.B.; Walker, M.G.; Rapp, K.; Meyer, B.C.; Zivin, J.A. Transcranial laser therapy for acute ischemic stroke: A pooled analysis of NEST-1 and NEST-2. Int. J. Stroke 2013, 8, 315–320. [Google Scholar] [CrossRef] [Green Version]
- Hacke, W.; Schellinger, P.D.; Albers, G.W.; Bornstein, N.M.; Dahlof, B.L.; Fulton, R.; Kasner, S.E.; Shuaib, A.; Richieri, S.P.; Dilly, S.G.; et al. Transcranial laser therapy in acute stroke treatment: Results of neurothera effectiveness and safety trial 3, a phase III clinical end point device trial. Stroke 2014, 45, 3187–3193. [Google Scholar] [CrossRef] [Green Version]
- Cassano, P.; Cassano, P.; Henderson, T.A. Reported side effects, weight and blood pressure, after repeated sessions of transcranial photobiomodulation. Photobiomodul. Photomed. Laser Surg. 2019, 37, 651–656. [Google Scholar] [CrossRef]
- Morries, L.D.; Cassano, P.; Henderson, T.A. Treatments for traumatic brain injury with emphasis on transcranial near-infrared laser phototherapy. Neuropsychiatr. Dis. Treat. 2015, 11, 2159–2175. [Google Scholar]
- Maiello, M.; Losiewicz, O.M.; Bui, E.; Spera, V.; Hamblin, M.R.; Marques, L.; Cassano, P. Transcranial photobiomodulation with near-infrared light for generalized anxiety disorder: A pilot study. Photobiomodul. Photomed. Laser Surg. 2019, 37, 644–650. [Google Scholar] [CrossRef]
- Iosifescu, D.V.; Norton, R.J.; Tural, U.; Mischoulon, D.; Collins, K.; Rette, D.; de Taboada, L.; Foster, S.; Cusin, C.; Yeung, A.; et al. Very low-level transcranial photobiomodulation for major depressive disorder: The ELATED-3 multicenter, randomized, sham-controlled trial. J. Clin. Psychiatry, 2022; in press. [Google Scholar]
- Levine, J.; Schooler, N.R. General versus specific inquiry with SAFTEE. J. Clin. Psychopharmacol. 1992, 12, 448. [Google Scholar] [CrossRef]
- Sheehan, D.V.; Lecrubier, Y.; Sheehan, K.H.; Amorim, P.; Janavs, J.; Weiller, E.; Hergueta, T.; Baker, R.; Dunbar, G.C. The mini-international neuropsychiatric interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J. Clin. Psychiatry 1998, 59 (Suppl. 20), 22–33. [Google Scholar]
- Busner, J.; Targum, S.D. The clinical global impressions scale: Applying a research tool in clinical practice. Psychiatry 2007, 4, 28–37. [Google Scholar]
- Hamilton, M. A rating scale for depression. J. Neurol. Neurosurg. Psychiatry 1960, 23, 56–62. [Google Scholar] [CrossRef] [Green Version]
- Jöbsis-VanderVliet, F.F.; Piantadosi, C.A.; Sylvia, A.L.; Lucas, S.K.; Keizer, H.H. Near-infrared monitoring of cerebral oxygen sufficiency: I. Spectra of cytochrome c oxidase. Neurol. Res. 1988, 10, 7–17. [Google Scholar] [CrossRef]
- Barrett, D.W.; Gonzalez-Lima, F. Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans. Neuroscience 2013, 230, 13–23. [Google Scholar] [CrossRef]
- Fava, M.; Evins, A.E.; Dorer, D.J.; Schoenfeld, D.A. The problem of the placebo response in clinical trials for psychiatric disorders: Culprits, possible remedies, and a novel study design approach. Psychother. Psychosom. 2003, 72, 115–127. [Google Scholar] [CrossRef]
- Morris, D.W.; Budhwar, N.; Husain, M.; Wisniewski, S.R.; Kurian, B.T.; Luther, J.F.; Kerber, K.; Rush, A.J.; Trivedi, M.H. Depression treatment in patients with general medical conditions: Results from the CO-MED trial. Ann. Fam. Med. 2012, 10, 23–33. [Google Scholar] [CrossRef] [Green Version]
- Ma, Y.; Balasubramanian, R.; Pagoto, S.L.; Schneider, K.L.; Hebert, J.R.; Phillips, L.S.; Goveas, J.S.; Culver, A.L.; Olendzki, B.C.; Beck, J.; et al. Relations of depressive symptoms and antidepressant use to body mass index and selected biomarkers for diabetes and cardiovascular disease. Am. J. Public Health 2013, 103, e34–e43. [Google Scholar] [CrossRef]
- Zivin, J.A.; Albers, G.W.; Bornstein, N.; Chippendale, T.; Dahlof, B.; Devlin, T.; Fisher, M.; Hacke, W.; Holt, W.; Ilic, S.; et al. Effectiveness and safety of transcranial laser therapy for acute ischemic stroke. Stroke 2009, 40, 1359–1364. [Google Scholar] [CrossRef] [Green Version]
- Salehpour, F.; Khademi, M.; Vahedifard, F.; Cassano, P. Transcranial photobiomodulation therapy for sexual dysfunction associated with depression or induced by antidepressant medications. Photonics 2022, 9, 330. [Google Scholar] [CrossRef]
- Cassano, P.; Dording, C.; Thomas, G.; Foster, S.; Yeung, A.; Uchida, M.; Hamblin, M.R.; Bui, E.; Fava, M.; Mischoulon, D.; et al. Effects of transcranial photobiomodulation with near-infrared light on sexual dysfunction. Lasers Surg. Med. 2019, 51, 127–135. [Google Scholar] [CrossRef]
- Schiffer, F.; Khan, A.; Bolger, E.; Flynn, E.; Seltzer, W.P.; Teicher, M.H. An effective and safe novel treatment of opioid use disorder: Unilateral transcranial photobiomodulation. Front Psychiatry 2021, 12, 713686. [Google Scholar] [CrossRef]
ELATED-2 | ELATED-3 | LIGHTEN-GAD | |
---|---|---|---|
Wavelength | 823 nm | 830 nm | 830 nm |
Irradiance | 33.2 mW/cm2 | 54.8 mW/cm2 | 30 mW/cm2 |
Average power | ~1.9 W | ~2 W | ~2.4 W |
Fluence | 60 J/cm2 | 65.8 J/cm2 | 36 J/cm2 |
Duration of t-PBM session | 20–30 min | 20 min | 20 min |
Treatment window | 57.4 cm2 | 35.8 cm2 | 80 cm2 |
Cumulative dose per session | 3.4 kJ | 2.3 kJ | 2.9 kJ |
Light placement (forehead) | F3, F4 | F3, F4, Fp1, Fp2 | F7, F8, Fp1, Fp2, Fpz |
ELATED-2 | ELATED-3 | LIGHTEN-GAD * | Total | |||||
---|---|---|---|---|---|---|---|---|
Variable | tPBM(n = 9) | Sham(n = 9) | tPBM(n = 27) | Sham(n = 23) | tPBM(n = 12) | tPBM(n = 48) | Sham(n = 32) | |
M(SD) | M(SD) | M(SD) | M(SD) | M(SD) | M(SD) | M(SD) | Statistic | |
Age | 47.3(11.1) | 49.3(14.2) | 39.0(16.6) | 48.2(16.5) | 30.25(14.9) | 38.5(16.2) | 46.2(15.5) | t(78) = 2.11, p = 0.02 |
HAM-D17 | 19.8(1.9) | 19.11(3.5) | 17.2(5.4) | 20.0(6.5) | 10.92(3.0) | 16.1(5.4) | 19.68(5.0) | t(77) = 2.94, p = 0.004 |
ELATED-2 | ELATED-3 | LIGHTEN-GAD | Total | |||||
Variable | tPBM(n = 9) | Sham(n = 9) | tPBM(n = 27) | Sham(n = 23) | tPBM(n = 12) | tPBM(n = 48) | Sham(n = 32) | Statistic |
Sex | ||||||||
Male | 4(44.4%) | 5(55.6%) | 8(29.6%) | 8(34.8%) | 4(33.3%) | 16(33.3%) | 13(40.6%) | X(1) = 0.44, p = 0.51 |
Female | 5(55.6%) | 4(44.4%) | 19(70.4%) | 15(65.2%) | 8(66.6%) | 32(66.7%) | 19(59.4%) | |
Race | ||||||||
White | 8(88.9%) | 8(88.9%) | 21(77.8%) | 20(87.0%) | 9(75.0%) | 38(79.2%) | 28(87.5%) | X(4) = 6.58, p = 0.16 |
Hatian, Black, or African American | 0(0.0%) | 1(11.1%) | 3(11.1%) | 2(8.7%) | 0(0.0%) | 3(6.3%) | 3(9.4%) | |
Asian | 1(11.1%) | 0(0.0%) | 2(7.4%) | 0(0.0%) | 3(25.0%) | 6(12.5%) | 0(0.0%) | |
White and Hatian Black or African American | 0(0.0%) | 0(0.0%) | 1(3.7%) | 0(0.0%) | 0(0.0%) | 1(2.1%) | 0(0.0%) | |
American Indian/Alaskan Native | 0(0.0%) | 0(0.0%) | 0(0.0%) | 1(4.3%) | 0(0.0%) | 0(0.0%) | 1(3.1%) | |
Ethnicity | ||||||||
Hispanic or LatinX | 0(0.0%) | 0(0.0%) | 3(11.1%) | 1(4.3%) | 2(16.7%) | 5(10.4%) | 1(3.1%) | X(3) = 5.39, p = 0.15 |
Not Hispanic or LatinX | 8(88.9%) | 9(100.0%) | 20(74.1%) | 22(95.7%) | 10(83.3%) | 38(79.2%) | 31(96.9%) | |
Jewish | 0(0.0%) | 0(0.0%) | 1(3.7%) | 0(0.0%) | 0(0.0%) | 1(2.1%) | 0(0.0%) | |
Not Reported | 1(11.1%) | 0(0.0%) | 3(11.1%) | 0(0.0%) | 0(0.0%) | 4(8.3%) | 0(0.0%) |
Predictor | b | 95% CI [LL, UL] | ß | t | p | R2 | p | F | df | p |
---|---|---|---|---|---|---|---|---|---|---|
Overall Model | 0.15 | 5 | 0.98 | |||||||
Age | 0.004 | [−0.05, 0.05] | 0.02 | 0.15 | 0.88 | 0.002 | 0.92 | |||
Sex | 0.30 | [−1.32, 1.91] | 0.04 | 0.37 | 0.72 | |||||
Energy Delivered | −0.95 | [−4.85, 2.95] | −0.06 | −0.49 | 0.63 | 0.005 | 0.63 | |||
Change in HAM-D17 | −0.31 | [−0.16, 0.10] | −0.06 | −0.47 | 0.64 | 0.01 | 0.64 | |||
HAM-D17xEnergy Delivered | −0.10 | [−0.65, 0.45] | −0.07 | −0.35 | 0.73 | 0.01 | 0.73 | |||
Overall Model (NIR Only) | 0.29 | 5 | 0.92 | |||||||
Age | −0.04 | [−0.12, 0.04] | −0.17 | 0.15 | −0.96 | 0.04 | 0.57 | |||
Sex | 0.85 | [−1.89, 3.59] | 0.11 | 0.37 | 0.53 | |||||
Energy Delivered | −2.13 | [−9.08, 4.83] | −0.11 | −0.62 | 0.54 | 0.05 | 0.54 | |||
Change in HAM-D17 | 0.002 | [−0.24, 0.25] | 0.003 | 0.02 | 0.99 | 0.05 | 0.99 | |||
HAM-D17xEnergy Delivered | −0.07 | [−1.22, 1.07] | −0.07 | −0.13 | 0.90 | 0.05 | 0.90 |
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Cassano, P.; Norton, R.; Caldieraro, M.A.; Vahedifard, F.; Vizcaino, F.; McEachern, K.M.; Iosifescu, D. Tolerability and Safety of Transcranial Photobiomodulation for Mood and Anxiety Disorders. Photonics 2022, 9, 507. https://doi.org/10.3390/photonics9080507
Cassano P, Norton R, Caldieraro MA, Vahedifard F, Vizcaino F, McEachern KM, Iosifescu D. Tolerability and Safety of Transcranial Photobiomodulation for Mood and Anxiety Disorders. Photonics. 2022; 9(8):507. https://doi.org/10.3390/photonics9080507
Chicago/Turabian StyleCassano, Paolo, Richard Norton, Marco Antonio Caldieraro, Farzan Vahedifard, Fernando Vizcaino, Kayla Marie McEachern, and Dan Iosifescu. 2022. "Tolerability and Safety of Transcranial Photobiomodulation for Mood and Anxiety Disorders" Photonics 9, no. 8: 507. https://doi.org/10.3390/photonics9080507