Journal of Pharmacy Practice and Pharmaceutical Sciences ISSN: 2652-2536 10.33513/PPPS/1901-16 Al-Achi A. J Pharm Pract Pharm Sci 2019(1): 75-76. OCIMUM

Editorial as a Dietary Supplement

Mental disorders account for 40% of causes of disabilities in the developing world as well as in the United States [1]. It is also estimated that approximately 25% of adult Americans suffer from some form of mental illness, including major depression, bipolar disorder, schizophrenia, and obsessive-compulsive disorder [1]. These disorders may be treated with antidepressant medications or lithium. Although the use of lithium is on the decline to treat mood disorders [2], lithium remains to be a successful treatment of affective disorders (unipolar, bipolar, and schizoaffective illness) in young and older patient populations alike [3,4]. It often produces positive results and augments antidepressant- Antoine Al-Achi* resistant unipolar major depressive disorder [5,6]. It is estimated that about College of Pharmacy and Health Sciences, 80% of patients with mania (i.e., bipolar) respond to lithium therapy in the Campbell University, USA acute phase [4]. Affective disorders are commonly associated with severe morbidity and mortality-related suicide [4,7]. Lithium therapy has been shown Received: 13 August 2019 to reduce the risk of suicide in patients with mood disorders, in particular, Accepted: 22 August 2019 those with unipolar and bipolar mood disorder patients [5,8]. A 12-hour Version of Record Online: 6 September 2019 plasma lithium concentration of 0.5-0.7 mmol/L has been established to be Citation the most effective [8]. This therapeutic range may be established by a daily lithium dose of 900 mg [6]. Although this therapeutic range of lithium does Al-Achi A (2019) Lithium as a Dietary Supplement. not produce significant side effects [3,8], it is considered to be narrow, and thus, J Pharm Pract Pharm Sci 2019(1): 75-76. it is subject to result in some form of toxicity (75% of patients on long-term lithium therapy will experience some toxic effect) [8]. Lithium neurotoxicity Correspondence should be addressed to Antoine Al-Achi, USA can occur within the therapeutic levels, which may include neuroleptic E-mail: [email protected] malignant syndrome (altered mental status, autonomic dysregulation, fever, and muscular stiffness) [8]. Elderly patients may be more susceptible to the Copyright neurotoxicity, and thus, they should be given a lower lithium dose to avoid it [9]. Much of the toxicity of lithium may be attributed to drug overdose, Copyright © 2019 Antoine Al-Achi. This is an dehydration, and pharmacokinetic interactions with other drugs (angiotensin open access article distributed under the Creative receptor blockers, non-steroidal anti-inflammatory drugs, and diuretics) [8]. Commons Attribution License which permits Lithium renal clearance can be reduced with age, and therefore, the dose unrestricted use, distribution, and reproduction of lithium should be lowered with advancing age in order to avoid toxicity in any medium, provided the original author and work is properly cited. [10]. Based on a Safety Data Sheet (SDS) available on the Internet [https:// www.nwmissouri.edu/naturalsciences/sds/l/Lithium%20carbonate.pdf], lithium is available as lithium salt with a solubility in water of 8.4 g/L at 20 °C. A 1 g/L solution in water produces a pH of 9.0-11.0 at room temperature. is the most common form of lithium salts available for therapy. Lithium side effects following a high dose include a dulled personality, memory loss, reduced emotions, tremors, and weight gain [1]. It is interesting to note that 80% of bipolar patients have some vitamin B deficiencies [1]. Although the role of side effects remains unclear with lithium therapy adherence, it is estimated that over 40% of patients who are on lithium therapy are classified as non-adherent [2]. Lithium is available on the market as capsules, solutions, immediate-release, and extended-release

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Citation: Al-Achi A (2019) Lithium as a Dietary Supplement. J Pharm Pract Pharm Sci 2019(1): 75-76. DOI:10.33513/PPPS/1901-16 tablets. A new pharmaceutical innovation on delivering lithium 2. Gitlin M (2016) Lithium side effects and toxicity: Prevalence carbonate was proposed by which six tablets of lithium (one and management strategies. J Bipolar Disord 24: 27. immediate-release and the others extended-release) were placed 3. Coppen A, Abou‐Saleh MT (1988) Lithium therapy: From inside a capsule. This dosage form was reported to provide a clinical trials to practical management. Acta Psychiatr Scand 24-hour extended-release delivery for lithium [11]. Lithium 78: 754-762. was reported to prevent or reduce neuropathic pain associated 4. Lepkifker E, Iancu I, Horesh N, Strous RD, Kotler M (2007) with the treatment of the chemotherapeutic agent Taxol [12]. Lithium therapy for unipolar and bipolar depression among the middle-aged and older adult patient subpopulation. Depress Dietary supplements of lithium are available on the market. Anxiety 24: 571-576. These include products-containing lithium in the form of a 5. Rihmer Z, Gonda X (2011) Antidepressant-Resistant depression liquid ionic form (500 mcg/10 drops), tablets (10 mg of lithium and antidepressant-associated suicidal behaviour: The role of orotate), and capsules (lithium orotate 5 mg; lithium aspartate underlying bipolarity. Depression Research and Treatment. 5-10 mg), among others. Although the dose of lithium in these supplements is much lower than that found in pharmaceuticals, 6. Alevizos B, Alevizos E, Leonardou A, Zervas I (2012) Low dosage lithium augmentation in venlafaxine resistant overdosing with the supplements can produce mild tremor depression: an open-label study. Psychiatriki 23: 143-148. with severe nausea and vomiting that may require emergency medical attention [13]. Also, supplementing with dietary 7. Edokpolo O, Fyyaz M (2012) Lithium toxicity and neurologic effects: Probable neuroleptic malignant syndrome resulting lithium products can cause drug/supplement interactions, and from lithium toxicity. Case Reports in Psychiatry. therefore, it must be communicated to health care providers. For instance, lithium interacts with the antibiotic metronidazole, 8. Coppen A (2000) Lithium in unipolar depression and the and replacement antibiotic must be given instead when needed prevention of suicide. J Clin Psychiatry 61: 52-56. [14]. The use of dietary lithium products by the public is 9. Arnaoudova MD (2014) Lithium toxicityin elderly-A case report commonly cited for its potential known positive effects on and discussion. Journal of IMAB 20: 519-522. depression and suicide prevention [15]. Moreover, lithium 10. Norman TR, Walker RG, Burrows GD (1984) Renal function is believed to enhance cognitive ability and to reduce the related changes in lithium kinetics. Clin Pharmacokinet 9: incidence of dementia [15]. Long-term treatment with lithium 349-353. in older adults who had amnestic mild cognitive impairment 11. Pietkiewicz P, Sznitowska M, Dorosz A, Lukasiak J (2003) showed a definite improvement in cognitive functions as well Lithium carbonate 24-hour extended-release capsule filled as modifications of cerebrospinal fluid biomarkers associated with 6 mm tablets. Boll Chim Farm 142: 69-71. with Alzheimer’s disease [16]. However, it should be noted that a significant lowering in kidney concentrating ability may be 12. Gao M, Yan X, H-R Weng (2013) Inhibition of glycogen synthase kinase 3beta activity with lithium prevents and encountered in the long-term lithium-treated patients [17]. In attenuates paclitaxel-induced neuropathic pain. Neuroscience the form of lithium orotate, lithium is readily available in its 254: 301-311. ionic form following its dissolution in water. According to an 13. Pauzé DK, Brooks DE (2007) Lithium toxicity from an internet SDS [http://materie-prime.farmalabor.it/sds/01412_en.pdf] dietary supplement. J Med Toxicol 3: 61-62. for lithium orotate, the salt is white crystalline powder with a neutral odor having a flashpoint greater than 300 °C. The salt 14. Van Weringh G, Uitvlugt EB, Ponjee GHM, M Jalink G (2017) is slightly soluble in water at room temperature. Incidentally, Confusion caused by dietary supplement lithium orotate. Tijdschrift Voor Psychiatrie 59: 234-237. the orotate ion can cross the blood-brain barrier more readily and quickly than the carbonate ion, and thus administering 15. Post RM (2018) The new news about lithium: An underutilized lithium as orotate is a better and more efficient way for therapy treatment in the United States. Neuropsychopharmacology 43: 1174-1179. [1]. The orotate form also allows a lower dose of lithium while reducing the possibility of side effects development [1]. 16. Forlenza OV, Radanovic M, TalibLL, Gattaz WF (2019) Clinical and biological effects of long-term lithium treatment in older In conclusion, the dietary supplement form of lithium (lithium adults with amnestic mild cognitive impairment: randomised orotate) appears to have some beneficial effects for maintaining clinical trial Br J Psychiatry 5: 1-7. a healthy mood provided the patient coordinates their use of 17. Dastych M, Synek O, Gottwaldová J (2019) Impact of long- this supplement with a primary health care provider. term Lithium treatment on renal function in patients with bipolar disorder based on novel biomarkers. J Clin Psychopharmacol References 39: 238-242. 1. Lakhan SE, Vieira KF (2008) Nutritional therapies for mental disorders. Nutr J 7: 2.

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