World health organization – depression • Depression is commonest psychiatric disorder affecting about 154 million people worldwide. • More than 90 percent of people who commit suicide have a diagnosable mental disorder, commonly a depressive disorder Despite advances in pharmacotherapy, a significant proportion of depressed patients are considered treatment-resistant. Poor compliance, side effects, or lack of desired effects are not uncommon with antidepressant medications. 2 To provide a comprehensive overview of the evidence based literature on Ayurvedic treatment of Depression with the clinical data including the studies on recent nutritional interventions and the neurobiological mechanism to mediate its beneficial effect. The PubMed, Medline, PsycInfo databases and other authentic websites were searched for the literature and published research articles related to Ayurvedic cure in depression. Author’s own research work evaluating the role of omega 3 fatty acids in etiopathogenesis and management of the depression has also been included in the present article. 35 clinically diagnosed patient using DSM IV diagnostic criteria for minor & major depressive illness were administered Kushmanda Ghrita : 20 ml in two divided doses Duration of treatment: 1 month Symptoms Scale Mean ± SD d t p BT AT HRSD 9.86±1.56 2.80±1.41 7.06±1.71 24.36 <0.001 HARS 6.09±1.24 1.29±1.06 4.79±1.07 26.20 <0.001 IMSD 5.05±1.10 5.80±1.05 0.74±1.01 4.35 <0.001 IMSID 3.22±0.80 3.74±0.98 0.51±0.89 3.43 <0.01 Rajni Chandre et al., AYU, 32(2), 2011 6 An open labeled randomized clinical trial involved 90 depressive patients (DSM IV diagnostic criteria for depression) were divided in three groups. Group Dose Duration Imipramine (n=30) 150 mg /day 3 months Sertaline (n=30) 150 mg /day Ayurvedic formulatuion: (n=30) Aqueous extract of Brahmi (Bacopa monnieri), Shankhapushpi (Convolvulus pluricaulis), Jyotishmati (Celastrus paniculatus), Jatamansi (Nardostacys Jatamansi) (equal amount) 1 gm in two divided doses Jyotsana Bhargva, Zafar Yab Khan, Jr of Clinical & Diagnostic Research, 2012, vol 6(2) 7 Effect on Hamilton Rating Scale for Depression & Side effects observed during treatment Groups (HRDS) BT AT p Imipramine 27.83±2.30 13.67±4.74* P<0.01 Sertaline 25.87±1.18 14.23±3.51* P<0.01 Ayurvedic formulation 25.33±1.22 14.60±2.11* P<0.01 Side effect Imipramine Sertaline Ayurvedic formulation Dry mouth 18 2 0 Weight gain 3 0 0 Urinary retention 4 2 0 Sedation 20 0 1 Agitation 3 0 0 Tremors 5 0 2 Tachycardia 12 1 0 Abdominal dicomfort 9 3 1 Nausea 0 8 0 Saxual dysfunction 4 2 0 Jyotsana Bhargva, Zafar Yab Khan, Jr of Clinical & Diagnostic Research, 2012, vol 6(2) 8 Nerve tissue possesses one of the highest concentrations of fatty acids in the body, with approximately 20% of the dry weight of the brain comprised of long-chain fatty acids. Essential for both the structure and function of nerve cells Omega 3s – ALA – alpha linolenic acid EPA – eicosapentaenoic acid DHA – docosahexaenoic acid PUFA Omega 6s – Lenoleic acid Gamma linoleic acid Dihomo gama linoleic acid Arachidonic acid Survey – OBSERVATION Depressed subjects N=130 (Diagnostic criteria: DSM-IV for Major depression) Ila Tanna, H M Chandola et al., 2012 Non-depressed healthy subjects ( IPGT & RA) N=100 Overall results of consumption of dietary articles by depressive patients and non-depressive healthy volunteers Parameter Diet containing Omega 3 Fatty acid Diet articles interfering with conversion of ALA to EPA & DHA 7/7/2014 Group Mean±SEM (MSC) Depressed 125.02±2.34 Non-depressed 165.61±4.45 Depressed 58.05±1.74 Non-depressed Ila Tanna, H M Chandola et al., 2012 t P S 8.59 <0.001 HS 3.71 <0.001 HS 48.54±1.84 12 Comparative effect of therapy over BDI Group < 50%  50% Total A 27.00 8.00 35 B B 12.00 33.00 45 12.00 33.00 45 C 12.00 8.00 20 A 27.00 8.00 35 C 12.00 8.00 X2 p S 19.78 <0.001 HS 6.04 <0.05 S 2.03 >0.05 NS 20 Ila Tanna, H M Chandola et al., 2012 14 Depression Imbalance of neuro transmitters Vacha Chitraka Daruharidra Daruharidra Ashwagandha, Vacha, Pippali, Maricha, Daruharidra Dopamine ↑ Nor epinephrine ↑ Serotonin ↑ Sleep problems ↓, Irritability↓, anxiety↓ Memory↑, appetite↑, loss of libido↓ Fatigue↓ depressed mood↓, Concentration↑, interest↑motivation↑ Pleasure↑, motivation↑ Ila Tanna, H M Chandola et al., 2012 Vacha: GABAnergic activity Antidepressant: Shunthi & Haridra Omega-3s & Mood disorder promote transmission of the chemical messengers Positive emotions (e.g., dopamine) Emotional stability (e.g., serotonin) BDNF Provides neuro protection, Enhances neurotransmission, Anti depressant effect bipolar disorder, unipolar depression, borderline personality disorder etc. Flax seed oil Omega 3 FA ALA Increases BDNF α - Lenolenic acid Rapidly diffuse from plasma to brain Induces hippocampal neurogenesis Sub-chronic treatment with ALA Improves synaptic plasticity and synaptogenesis Induces antidepressant like behavior in animal models Ila Tanna, H M Chandola et al., 2012 Which can also be related to additive or synergic interactions with .serotonin, norepinephrine or dopamine pathways  Physical and mental relaxation causes 1. decrease in level of brain cortisone and adrenaline 2. synchronization of the brain wave (alpha waves) 3. strengthening of mind and spirit which continuing even after the relaxation.  A study , “Psychoneuroimmunologic Effects of Ayurvedic Oil-Dripping Treatment” shows that Shirodhara has  anxiolytic and  ASC (Altered State of Consciousness) - inducing effects, and  promotes a decrease of noradrenaline and exhibits a sympatholytic effect, resulting in the activation of peripheral foot skin circulation and immuno-potentiation. Kazuo et al., The Alternative & Complementary Medicine, 2008 There are reasonable evidences related to Ayurveda for its use as first line treatment in mild and moderate cases of major depression and as a second line monotherapy or augmentation to western pharmacotherapy in moderate to severe depression. Panchakarma procedures like Shirodhara, Nasya, etc. provide beneficial effect. Omega 3 fatty acid deficiency is one of the contributing factor to depression and Atasi taila can be used as monotherapy or as an adjuvant to other Ayurvedic drugs to correct the omega 3 deficiencies. 1. Kornstein SG, Schneider RK. Clinical features of treatment-resistant depression. J Clin Psychiatry 2001;62:18-25. 2. Ikemoto A, Nitta A, Furulwa S,Ohishi M, Nakamura A, Fujii Y, Okuyama H: Dietary omega 3 fatty acid deficiency decreases nerve growth factor content in rat hippocampus. Neurosci Lett 2000; 285: 99-102 3. Rajni Chandre et al., Clinical evaluation of Kushmanda Ghrita in the management of depressive illness; AYU, vol. 32(2), 2011 4. Jyotsana Bhargva, Zafar Yab Khan, Comparative evaluation of the efficacy and side effects of Imipramine, Sertaline and an Ayurvedic formulation in patients of depression; Jr of Clinical & Diagnostic Research, vol 6(2), 2012. 5. Sunilkumar M.Chabanur, Narayan Prakash, “A Clinical Study on Shireeshadi Yoga in the Management of Kaphaja Unmada w.s.r.to Depressive Disorders”, MD thesis, Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore, 2011 6. Ila Tanna, H.M. Chandola, Rajesh Kukmar, Role of Omega 3 fatty acids in etiopathogenesis of depression and evaluation of flax seed (Linum usitatissimum Linn.) oil as an adjuvant to Ashwagandhadyarishta in its management, Ph.D. Thesis, Dept. of Rog Nidan & Vikriti Vigyan, IPGT & RA, GAU, Jamnagar, 2013. 7. Delion S, Chalon S, Guilloteau D, Besnard JC, Durand G (1996). Alpha lenolenic acid dietary deficiency alters age related changes of dopamineric and serotonergic neurotransmission in the rat frontal cortex. J Neurochem 66:1582-1591. 8. S, Chalon S, Guilloteau D, Besnard JC, Durand G (1994). Chronic dietary alpha lenolenic acid deficiency alters dopamineric and serotonergic neurotransmission in the rats. J Nutr 124:246-2476. 9. Dermar Jr., Ma,K., Chang, L, Bell. J.M., Rapoport, S.I., 2005. Alpha lenolenic acid does not contribute appreciably to docosahexanoic acid within brain phospholipids of adult rats fed a diet enriched in docosahexaenoic acid. J. Neurochem. 94, 1063-1076. 10. Kazuo Uebaba, Feng-Hao Xu, Hiroko Ogawa, Takashi Tatsuse, Bing-Hong Wang, Tatsuya Hisajima, Sonia Venkatraman. The Journal of Alternative and Complementary Medicine. December 2008, 14(10): 1189-1198. doi:10.1089/acm.2008.0273. 11. Ila Tanna, H.M.Chandola, Therapeutic Efficacy of Various Shirodhara on Stress induced insomnia; Ayurveda Sameekshawa, Volume II, Part VII, Sri Lanka, 2011. 12. http://www.brightthub.com/health/alternative-medicine/articles/24593.aspx retrived on 1/9/2010