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{{CMG}}
==Overview==
Compounds of the element [[lithium]] are commonly used as a [[psychiatry|psychiatric]] [[medication]]. A number of [[Salt (chemistry)|salts]] of lithium are used as [[mood stabilizer|mood-stabilizing]] [[Medication|drugs]], primarily in the treatment of [[bipolar disorder]], where they have a role in the treatment of [[Clinical depression|depression]] and particularly of [[mania]], both acutely and in the long term. As a mood stabilizer, lithium is probably more effective in preventing mania than depression, and reduces the risk of suicide in bipolar patients.<ref>{{cite journal |pages=625–39 |doi=10.1111/j.1399-5618.2006.00344.x |title=Decreased risk of suicides and attempts during long-term lithium treatment: A meta-analytic review |year=2006 |last1=Baldessarini |first1=Ross J |last2=Tondo |first2=Leonardo |last3=Davis |first3=Paula |last4=Pompili |first4=Maurizio |last5=Goodwin |first5=Frederick K |last6=Hennen |first6=John |journal=Bipolar Disorders |volume=8 |issue=5p2 |pmid=17042835}}</ref> In depression alone (unipolar disorder), lithium can be used to augment other antidepressants. [[Lithium carbonate]] (Li<sub>2</sub>CO<sub>3</sub>), sold under several trade names, is the most commonly prescribed, while [[lithium citrate]] (Li<sub>3</sub>C<sub>6</sub>H<sub>5</sub>O<sub>7</sub>) is also used in conventional pharmacological treatments. [[Lithium sulfate]] (Li<sub>2</sub>SO<sub>4</sub>) has been presented as an alternative.
Upon ingestion, lithium becomes widely distributed in the [[central nervous system]] and interacts with a number of [[neurotransmitter]]s and [[receptor (biochemistry)|receptors]], decreasing [[norepinephrine]] (noradrenaline) release and increasing [[serotonin]] synthesis.
==Medical uses==
Lithium treatment is used to treat [[mania]] in [[bipolar disorder]]. Initially, lithium is often used in conjunction with [[antipsychotic drugs]] as it can take up to a month for it to have an effect. Lithium is also used as [[prophylaxis]] for [[depression (mood)|depression]] and mania in bipolar disorder. It is sometimes used for other psychiatric disorders, such as [[cycloid psychosis]] and [[major depressive disorder]].<ref>{{cite book
|last=Mash
|first=Eric J.
|coauthors=Russell A. Barkley
|title=Treatment of childhood disorders
|publisher=[[Guilford Press]]
|year=2006
|page=443
|url=http://books.google.com/?id=KCZqs_NlfmQC
|isbn=1-57230-921-0
}}</ref><ref>{{cite book
|last=Schatzberg
|first=Alan F.
|coauthors=Jonathan O. Cole, Charles DeBattista
|title=Manual of clinical psychopharmacology
|publisher=[[American Psychiatric Publishing]]
|year=2007
|page=267
|url=http://books.google.com/?id=NvT0l6iL5IQC
|isbn=1-58562-317-2
}}</ref> Lithium possesses a very important antisuicidal effect not shown in other stabilizing medications such as antiseizure drugs.<ref name="ReferenceA">{{cite journal|url=https://ww1.cpa-apc.org/Publications/Archives/CJP/2003/august/muller.asp |title=The Antisuicidal and Mortality-Reducing Effect of Lithium Prophylaxis: Consequences for Guidelines in Clinical Psychiatry |pmid=12971012|year=2003|last1=Müller-Oerlinghausen|first1=B|last2=Berghöfer|first2=A|last3=Ahrens|first3=B|volume=48|issue=7|pages=433–9|journal=Canadian Journal of Psychiatry}}</ref><ref>{{cite journal|doi=10.1146/annurev.pharmtox.011008.145557|title=Lithium's Antisuicidal Efficacy: Elucidation of Neurobiological Targets Using Endophenotype Strategies|year=2009|last1=Kovacsics|first1=Colleen E.|last2=Gottesman|first2=Irving I.|last3=Gould|first3=Todd D.|journal=Annual Review of Pharmacology and Toxicology|volume=49|pages=175–198|pmid=18834309}}</ref> Nonpsychiatric applications are limited; however, its use is well established in the prophylaxis of some headaches related to [[cluster headache]]s (trigeminal autonomic cephalgias), particularly [[hypnic headache]]. An Italian pilot study in humans conducted in 2005–06 suggested lithium may improve outcomes in the [[neurodegenerative disease]] [[amyotrophic lateral sclerosis|amyotrophic lateral sclerosis (ALS)]].<ref>{{cite web
|title=Lithium Slows ALS Progression In Study
|publisher=[[Muscular Dystrophy Association]]
|date=2008-02-04
|url=http://www.als-mda.org/research/news/080204Lithium_slows_ALS.html
|accessdate=2009-06-23}}
</ref><ref>{{cite journal |doi=10.1073/pnas.0708022105 |title=Lithium delays progression of amyotrophic lateral sclerosis |year=2008 |last1=Fornai |first1=F. |last2=Longone |first2=P. |last3=Cafaro |first3=L. |last4=Kastsiuchenka |first4=O. |last5=Ferrucci |first5=M. |last6=Manca |first6=M. L. |last7=Lazzeri |first7=G. |last8=Spalloni |first8=A. |last9=Bellio |first9=N. |journal=Proceedings of the National Academy of Sciences |volume=105 |issue=6 |pages=2052}}</ref>
However, a randomised, double-blind, placebo-controlled trial comparing the safety and efficacy of lithium in combination with [[riluzole]] for treatment of ALS failed to demonstrate a benefit as compared to a combination therapy over riluzole alone.<ref>{{cite journal |doi=10.1016/S1474-4422(10)70068-5 |title=Safety and efficacy of lithium in combination with riluzole for treatment of amyotrophic lateral sclerosis: A randomised, double-blind, placebo-controlled trial |year=2010 |last1=Aggarwal |first1=Swati P |last2=Zinman |first2=Lorne |last3=Simpson |first3=Elizabeth |last4=McKinley |first4=Jane |last5=Jackson |first5=Katherine E |last6=Pinto |first6=Hanika |last7=Kaufman |first7=Petra |last8=Conwit |first8=Robin A |last9=Schoenfeld |first9=David |journal=The Lancet Neurology |volume=9 |issue=5 |pages=481}}</ref>
Lithium is sometimes used as an augmenting agent to increase the benefits of standard drugs used for unipolar depression. Lithium treatment was previously considered to be unsuitable for children; however, more recent studies show its effectiveness for treatment of early-onset bipolar disorder in children as young as eight. The required dosage (15–20 mg per kg of body weight) is slightly less than the toxic level, requiring blood levels of lithium to be monitored closely during treatment. To prescribe the correct dosage, the patient's entire medical history, both physical and psychological, is sometimes taken into consideration. The starting dosage of lithium should be 400–600 mg given at night and increased weekly depending on serum monitoring.<ref>Semple, David"oxford hand book of psychiatry" oxford press. 2005.{{page needed|date=January 2012}}</ref>
Those who use lithium should receive regular serum level tests and should monitor thyroid and kidney function for abnormalities, as it interferes with the regulation of [[sodium]] and [[water]] levels in the body, and can cause [[dehydration]]. Dehydration, which is compounded by heat, can result in increasing lithium levels. The dehydration is due to lithium inhibition of the action of [[antidiuretic hormone]], which normally enables the kidney to reabsorb water from urine. This causes an inability to concentrate urine, leading to consequent loss of body water and thirst.<ref>Healy D. 2005. ''Psychiatric Drugs Explained''. 4th ed. Churchhill Livingstone: London.{{page needed|date=January 2012}}</ref>
High doses of [[haloperidol]], [[fluphenazine]], or [[flupenthixol]] may be hazardous when used with lithium; irreversible [[toxic encephalopathy]] has been reported.<ref>Case reports: ({{Cite pmid|6415823}})({{Cite pmid|9296146}})</ref>
Lithium salts have a narrow therapeutic/toxic ratio, so should not be prescribed unless facilities for monitoring [[Blood plasma|plasma]] concentrations are available. Patients should be carefully selected. Doses are adjusted to achieve plasma concentrations of 0.4<ref>The UK Electronic Medical Compendium recommends 0.4–0.8 mmol/l plasma lithium level in adults for prophylaxis of recurrent affective bipolar manic-depressive illness [http://www.medicines.org.uk/emc/document.aspx?documentId=1239 Camcolit 250 mg Lithium Carbonate] Revision 2 December 2010, Retrieved 5 May 2011</ref><ref>One study ({{Cite pmid|8831438}}) concluded a "low" dose of 0.4–0.6 mmol/L serum lithium treatment for patients with bipolar 1 disorder had less side effects, but a higher rate of relapse, than a "standard" dose of 0.8–1.0 mmol/l. However, a reanalysis of the same experimental data ({{Cite pmid|12091193}}) concluded the higher rate of relapse for the "low" dose was due to abrupt changes in the lithium serum levels{{synthesis-inline|date=January 2012}}</ref> to 1.2 mmol Li<sup>+</sup>/l (lower end of the range for maintenance therapy and elderly patients, higher end for pediatric patients) on samples taken 12 hours after the preceding dose. Overdosage, usually with plasma concentrations over 1.5 mmol Li<sup>+</sup>/l, may be fatal, and toxic effects include [[tremor]], [[ataxia]], [[dysarthria]], [[pathologic nystagmus|nystagmus]], [[renal failure|renal impairment]], confusion, and [[convulsion]]s. If these potentially hazardous signs occur, treatment should be stopped, plasma lithium concentrations redetermined, and steps taken to reverse lithium toxicity.
Lithium toxicity is compounded by sodium depletion. Concurrent use of [[diuretics]] that inhibit the uptake of sodium by the [[distal tubule]] (e.g. [[thiazides]]) is hazardous and should be avoided because this can cause increased resorption of lithium in the [[proximal convoluted tubule]], leading to elevated, potentially toxic levels. In mild cases, withdrawal of lithium and administration of generous amounts of sodium and fluid will reverse the toxicity. Plasma concentrations in excess of 2.5 mmol Li<sup>+</sup>/l are usually associated with serious toxicity requiring emergency treatment. When toxic concentrations are reached, there may be a delay of one or two days before maximum toxicity occurs.
In long-term use, therapeutic concentrations of lithium have been thought to cause [[Histology|histological]] and functional changes in the kidney. The significance of such changes is not clear, but is of sufficient concern to discourage long-term use of lithium unless it is definitely indicated. Doctors may change a bipolar patient's medication from lithium to another mood-stabilizing drug, such as [[valproic acid|valproate]] (Depakote), if problems with the kidneys arise. An important potential consequence of long-term lithium use is the development of renal [[diabetes insipidus]] (inability to concentrate urine). Patients should therefore be maintained on lithium treatment after three to five years only if, on assessment, benefit persists. Conventional and [[sustained-release]] tablets are available. Preparations vary widely in [[bioavailability]], and a change in the formulation used requires the same precautions as initiation of treatment. There are few reasons to prefer any one simple salt of lithium; the carbonate has been the more widely used, but the citrate is also available.
Lithium may be used as a treatment of seborrhoeic dermatitis (lithium gluconate 8% gel). In addition, lithium has been shown to increase production of white blood cells in the [[bone marrow]] and might be indicated in patients suffering from [[leukopenia]].<ref>{{cite journal
|last=Vieweg
|first=W. V. R.
|coauthors=Yank, Rowe, Hovermale, Clayton
|date=Fall 1986
|title=Increase in White Blood Cell Count and Serum Sodium Level Following the Addition of Lithium to Carbamazephine Treatment among three chronically Psychotic male Patients with disturbed Affective States
|journal=[[Psychiatric Quarterly]]
|volume=583
|page=213
|url=http://resources.metapress.com/pdf-preview.axd?code=u11w152782481762&size=largest
|accessdate=2010-04-20
}}</ref>
A limited amount of evidence suggests lithium may contribute to treatment of substance abuse for some dual-disorder patients.<ref>{{Cite pmid|17984856}}</ref><ref>{{Cite pmid|17156154}}</ref><ref>{{Cite pmid|16961421}}</ref>
In 2009, Japanese researchers at [[Oita University]] reported low levels of naturally occurring lithium in drinking water supplies reduced suicide rates.<ref>{{cite journal |pmid=19407280 |year=2009 |last1=Ohgami |first1=H |last2=Terao |first2=T |last3=Shiotsuki |first3=I |last4=Ishii |first4=N |last5=Iwata |first5=N |title=Lithium levels in drinking water and risk of suicide |volume=194 |issue=5 |pages=464–5; discussion 446 |doi=10.1192/bjp.bp.108.055798 |journal=The British journal of psychiatry : the journal of mental science}}</ref> A previous report had found similar data in the American state of [[Texas]].<ref>{{cite journal |pmid=18363457 |year=2008 |last1=Gonzalez |first1=R |last2=Bernstein |first2=I |last3=Suppes |first3=T |title=An investigation of water lithium concentrations and rates of violent acts in 11 Texas counties: Can an association be easily shown? |volume=69 |issue=2 |pages=325–6 |journal=The Journal of clinical psychiatry}}</ref> In response, psychiatrist [[Peter D. Kramer|Peter Kramer]] raised the hypothetical possibility of adding lithium to drinking water as a mineral supplement rather than as a therapeutic drug.<ref>[http://www.doublex.com/section/health-science/listening-lithium Listening to Lithium] Sept 9. 2009</ref> (The therapeutic dosage of lithium carbonate (tablets and capsules) or citrate (liquid) "usually ranges from 900 - 1,200 mg/day" and is adjusted according to patient response and blood levels.<ref>[http://www.nami.org/Template.cfm?Section=About_Medications&Template=/TaggedPage/TaggedPageDisplay.cfm&TPLID=51&ContentID=20820 National Alliance on Mental Illness, Medications]</ref>) This is analogous to [[niacin]], where a low dose in multivitamin pills is taken as a vitamin supplement to prevent the niacin deficiency disease [[pellagra]], but a high dose is prescribed as a therapeutic drug to raise [[high-density lipoprotein]] ("good" cholesterol) levels.
==Mechanism of action==
Unlike other [[psychoactive drugs]], Li<sup>+</sup> typically produces no obvious psychotropic effects (such as [[euphoria (emotion)|euphoria]]) in normal individuals at therapeutic concentrations. Li<sup>+</sup> possibly produces its effects by interacting with the transport of monovalent or divalent [[cations]] in [[neurons]]. However, because it is a poor substrate at the [[sodium pump]], it cannot maintain a [[membrane potential]] and only sustains a small gradient across [[biological membranes]]. Li<sup>+</sup> is similar enough to Na<sup>+</sup> that under experimental conditions, it can replace Na<sup>+</sup> for production of a single [[action potential]] in [[neuron]]s.
Recent research suggests three different mechanisms which may or may not act together to deliver the mood-stabilizing effect of this ion.<ref>{{cite journal |author=Jope RS |title=Anti-bipolar therapy: mechanism of action of lithium |journal=Mol. Psychiatry |volume=4 |issue=2 |pages=117–128 |year=1999|pmid=10208444 |doi= 10.1038/sj.mp.4000494}}</ref> The excitatory [[neurotransmitter]] [[glutamate]] could be involved in the effect of lithium as other mood stabilizers, such as [[valproate]] and [[lamotrigine]], exert influence over glutamate, suggesting a possible biological explanation for mania. The other mechanisms by which lithium might help to regulate mood include the alteration of [[gene expression]].<ref>{{cite journal |author=Lenox RH, Wang L |title=Molecular basis of lithium action: integration of lithium-responsive signaling and gene expression networks |journal=Mol. Psychiatry |volume=8 |issue=2 |pages=135–44 |year=2003 |month=February |pmid=12610644 |doi=10.1038/sj.mp.4001306}}</ref>
Lithium may also increase the release of [[serotonin]] by neurons in the brain.<ref>{{cite pmid|10481837}}</ref> In vitro studies performed on serotonergic neurons from rat [[raphe nuclei]] have shown that when these neurons are treated with lithium, [[serotonin]] release is enhanced during a [[depolarization]] compared to no lithium treatment and the same depolarization.<ref>{{cite pmid|19840776}}</ref>
An unrelated mechanism of action has been proposed in which lithium deactivates the [[GSK3B|GSK3β]] enzyme.<ref name="pmid8710892">{{cite journal | author = Klein PS, Melton DA | title = A molecular mechanism for the effect of lithium on development | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 16 | pages = 8455–9 | year = 1996 | month = August | pmid = 8710892 | pmc = 38692 | doi = 10.1073/pnas.93.16.8455 }}</ref> This enzyme normally [[phosphorylation|phosphorylates]] the [[Rev-ErbA alpha|Rev-Erbα]] transcription factor protein stabilizing it against degradation. Rev-Erbα in turn represses [[ARNTL|BMAL1]], a component of the [[circadian clock]]. Hence, lithium by inhibiting GSK3β causes the degradation of Rev-Erbα and increases the expression of BMAL which dampens the circadian clock<ref name="pmid16484495">{{cite journal | author = Yin L, Wang J, Klein PS, Lazar MA | title = Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock | journal = Science | volume = 311 | issue = 5763 | pages = 1002–5 | year = 2006 | month = February | pmid = 16484495 | doi = 10.1126/science.1121613 | laysummary = http://www.the-scientist.com/news/display/23129/ | laysource = The Scientist }}</ref> Through this mechanism, lithium is able to block the resetting of the "master clock" inside the brain; as a result, the body's natural cycle is disrupted. When the cycle is disrupted, the routine schedules of many functions (metabolism, sleep, body temperature) are disturbed. Lithium may thus restore normal brain function after it is disrupted in some people.
Several authors proposed that pAp-phosphatase could be one of the therapeutic targets of lithium.<ref>York JD et al. (1995) "Definition of a metal-dependent/Li+-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure". ''Proc. Natl. Acad. Sci. U.S.A''. '''92''', 5149-5153</ref><ref>Yenush Let al. (2000) "A novel target of lithium therapy". ''FEBS Lett''. '''467''', 321-325</ref> This hypothesis was supported by the low Ki of lithium for human pAp-phosphatase compatible within the range of therapeutic concentrations of lithium in the plasma of patients (0.8–1 mM). Importantly, the Ki of human pAp-phosphatase is ten times lower than that of GSK3β (glycogen synthase kinase 3β). Inhibition of pAp-phosphatase by lithium leads to increased levels of pAp (3′-5′ phosphoadenosine phosphate), which was shown to inhibit [[PARP-1]]<ref>Toledano E et al. "3'-5' phosphoadenosine phosphate is an inhibitor of PARP-1 and a potential mediator of the lithium-dependent inhibition of PARP-1 in vivo". ''Biochem J''. 2012 '''443'''(2):485-90. [http://www.ncbi.nlm.nih.gov/pubmed/22240080]</ref>
Another mechanism proposed in 2007 is that lithium may interact with [[nitric oxide]] (NO) signalling pathway in the central nervous system, which plays a crucial role in the neural plasticity. <!--Ghasemi et al. (2008, 2009) have shown that -->The NO system could be involved in the antidepressant effect of lithium in the Porsolt forced swimming test in mice.<ref name="pmid17728109">{{cite journal | author = Ghasemi M, Sadeghipour H, Mosleh A, Sadeghipour HR, Mani AR, Dehpour AR | title = Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test | journal = Eur Neuropsychopharmacol | volume = 18 | issue = 5 | pages = 323–32 | year = 2008 | month = May | pmid = 17728109 | doi = 10.1016/j.euroneuro.2007.07.011 }}</ref><ref name="pmid19166880">{{cite journal | author = Ghasemi M, Sadeghipour H, Poorheidari G, Dehpour AR | title = A role for nitrergic system in the antidepressant-like effects of chronic lithium treatment in the mouse forced swimming test | journal = Behav. Brain Res. | volume = 200 | issue = 1 | pages = 76–82 | year = 2009 | month = June | pmid = 19166880 | doi = 10.1016/j.bbr.2008.12.032 }}</ref> It was also reported that NMDA receptor blockage augments antidepressant-like effects of lithium in the mouse forced swimming test,<ref name="pmid19351802">{{cite journal | author = Ghasemi M, Raza M, Dehpour AR | title = NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test | journal = J. Psychopharmacol. (Oxford) | volume = 24 | issue = 4 | pages = 585–94 | year = 2010 | month = April | pmid = 19351802 | doi = 10.1177/0269881109104845 }}</ref> indicating the possible involvement of NMDA receptor/NO signaling in the action of lithium in this animal model of [[learned helplessness]].
[[Lithium]] treatment has been found to inhibit the enzyme [[inositol monophosphatase]], leading to higher levels of inositol triphosphate.<ref name="pmid9588758">{{cite journal | author = Einat H, Kofman O, Itkin O, Lewitan RJ, Belmaker RH | title = Augmentation of lithium's behavioral effect by inositol uptake inhibitors | journal = J Neural Transm | volume = 105 | issue = 1 | pages = 31–8 | year = 1998 | pmid = 9588758 | doi = 10.1007/s007020050035 }}</ref> This effect was enhanced further with an inositol triphosphate [[reuptake inhibitor]]. [[Inositol]] disruptions have been linked to memory impairment and [[Depression (mood)|depression]].
==Side effects==
The most common side effects are an overall dazed feeling and a fine [[tremor]] of hands. These side effects are generally present during the length of the treatment, but can sometimes disappear in certain patients. Other common side effects, such as nausea and headache, can be generally remedied by a higher intake of water. Lithium unbalances electrolytes; to counteract this, increased water intake is recommended.
According to an Australian study, "The incidence of [[hypothyroidism]] is six-fold higher in patients on lithium as compared to the general population. Hypothyroidism in turn increases the likelihood of developing clinical depression." <ref>[http://www.australianprescriber.com/magazine/36/1/18/21 Safe and effective use of lithium] Australian Prescriber</ref>
Lithium is known to be responsible for 1-2kg of weight gain.<ref>[http://www.australianprescriber.com/magazine/36/1/18/21 Safe and effective use of lithium] Australian Prescriber</ref> Weight gain may be a source of low self-esteem for the clinically depressed.<ref>
{{cite book
|last = Sperner-Unterweger
|first = Barbara
|coauthors = W. Wolfgang Fleischhacker, Wolfgang P. Kaschka
|title = Psychoneuroimmunology
|publisher = [[Karger Publishers]]
|year = 2001
|page = 22
|url = http://books.google.com/?id=Q0xJfkY5VRUC
|isbn =3-8055-7262-X}}
</ref> Because lithium competes with the receptors for the [[antidiuretic hormone]] in the kidney, it increases water output into the urine, a condition called nephrogenic [[diabetes insipidus]]. Clearance of lithium by the kidneys is usually successful with certain diuretic medications, including [[amiloride]] and [[triamterene]].<ref>{{cite journal |pmid=2516883 |year=1989 |last1=Wetzels |first1=JF |last2=Van Bergeijk |first2=JD |last3=Hoitsma |first3=AJ |last4=Huysmans |first4=FT |last5=Koene |first5=RA |title=Triamterene increases lithium excretion in healthy subjects: Evidence for lithium transport in the cortical collecting tubule |volume=4 |issue=11 |pages=939–42 |journal=Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}}</ref> It increases the appetite and thirst ("polydypsia") and reduces the activity of [[thyroid hormone]] ([[hypothyroidism]]).<ref>
{{cite book
|last = Keshavan
|first = Matcheri S.
|coauthors = John S. Kennedy
|title = Drug-induced dysfunction in psychiatry
|publisher = [[Taylor & Francis]]
|year = 2001
|page = 305
|url = http://books.google.com/?id=pol0204fqjIC
|isbn =0-89116-961-X}}
</ref><ref>[http://bipolar.about.com/cs/sfx/a/sfx_lithium.htm Side Effects – Lithium / Various Brand Names – Bipolar Disorder Medications]</ref><ref>[http://www.psycheducation.org/hormones/Insulin/weightgain.htm Bipolar Medications and Weight Gain]</ref><ref>[http://www.netnutritionist.com/fa12.htm Nutrition Articles – The Relationship between Weight Gain and Medications for Depression and Seizures]</ref><ref>[http://www.nrls.npsa.nhs.uk/resources/patient-safety-topics/medication-safety/?entryid45=65426 Safer lithium therapy]. NHS National Patient Safety Agency. Issue date: 1 December 2009</ref> The latter can be corrected by treatment with [[thyroxine]]. Lithium is also believed to permanently affect renal function, although this does not appear to be common.<ref>
{{cite journal
|doi = 10.1038/ki.2009.433
|last = Bendz
|first = Hans
|coauthors = Schön, Attman, Aurell
|date = February 1, 2010
|title = Renal failure occurs in chronic lithium treatment but is uncommon
|journal = Kidney International
|volume = 77
|issue = 3
|pmid = 19940841
|pages = 219–24
}}
</ref>
Lithium is a well-known cause of [[physiologic nystagmus#Types|downbeat nystagmus]],<ref>
{{cite journal
|doi = 10.1212/01.WNL.0000042787.51461.D1
|last = Lee
|first = Michael S.
|coauthors = Lessell, Simmons
|date = January 28, 2003
|title = Lithium-induced periodic alternating nystagmus
|journal = [[Neurology (journal)]]
|volume = 60
|issue = 2
|page = 344
|pmid = 12552061
}}
</ref> which may be permanent or require several months of abstinence for improvement.<ref>
{{cite journal
|doi = 10.1001/archneur.1988.00520330112019
|last = Williams
|first = Douglas P.
|coauthors = Jack Rogers and B. Todd Troost
|date = September 1988
|title = Lithium-Induced Downbeat Nystagmus
|journal = [[Archives of Neurology]]
|volume = 45
|issue = 9
|pages = 1022–1023
|pmid = 3137915
}}
</ref>
Most side effects of lithium are dose-dependent. The lowest effective dose is used to limit the risk of side effects.
=== Teratogenicity ===
Lithium is also a [[teratogen]], causing birth defects in a small number of newborn babies.<ref name="Shepard-2002">{{Cite journal|last1 = Shepard|first1 = TH.|last2 = Brent|first2 = RL.|last3 = Friedman|first3 = JM.|last4 = Jones|first4 = KL.|last5 = Miller|first5 = RK.|last6 = Moore|first6 = CA.|last7 = Polifka|first7 = JE.|title = Update on new developments in the study of human teratogens|journal = Teratology|volume = 65|issue = 4|pages = 153–61|year = 2002|doi = 10.1002/tera.10032|pmid = 11948561}}</ref> [[Case report]]s and several [[Retrospective cohort study|retrospective studies]] have demonstrated possible increases in the rate of a congenital heart defect known as [[Ebstein's anomaly]], if taken during a woman's pregnancy.<ref name="pmid18982835">{{cite journal |pmid=18982835 |year=2008 |last1=Yacobi |first1=S |last2=Ornoy |first2=A |title=Is lithium a real teratogen? What can we conclude from the prospective versus retrospective studies? A review |volume=45 |issue=2 |pages=95–106 |journal=The Israel journal of psychiatry and related sciences}}</ref> As a consequence, fetal [[echocardiography]] is routinely performed in pregnant women taking lithium to exclude the possibility of cardiac anomalies. [[Lamotrigine]] seems to be a possible alternative to lithium in pregnant women.<ref name="pmid18982835" /> [[Gabapentin]]<ref name="pmid12791334">{{cite journal |pmid=12791334 |year=2003 |last1=Montouris |first1=G |title=Gabapentin exposure in human pregnancy: Results from the Gabapentin Pregnancy Registry |volume=4 |issue=3 |pages=310–7 |journal=Epilepsy & behavior : E&B |doi=10.1016/S1525-5050(03)00110-0}}</ref> and [[clonazepam]]<ref name="pmid11340418">{{cite journal |pmid=11340418 |year=2001 |last1=Weinstock |first1=L |last2=Cohen |first2=LS |last3=Bailey |first3=JW |last4=Blatman |first4=R |last5=Rosenbaum |first5=JF |title=Obstetrical and neonatal outcome following clonazepam use during pregnancy: A case series |volume=70 |issue=3 |pages=158–62 |journal=Psychotherapy and psychosomatics}}</ref> are also indicated as antipanic medications during the childbearing years and during [[pregnancy]]. [[Valproic acid]] and [[carbamazepine]] also tend to be associated with teratogenicity.
===Dehydration===
Dehydration in patients taking lithium salts can be very hazardous, especially when combined with lithium induced nephrogenic [[diabetes insipidus]] with polyuria. Such situations include preoperative fluid regimen or other fluid inaccessibility, warm weather conditions, sporting events, and hiking.
Another danger is that rapid hydration may very quickly produce hyponatremia with its danger of toxic lithium concentrations in plasma.
===Overdose===
Lithium toxicity may occur in persons taking excessive amounts either accidentally or intentionally on an acute basis or in patients who accumulate high levels during ongoing chronic therapy. The manifestations include nausea, [[emesis]], diarrhea, [[asthenia]], [[ataxia]], confusion, lethargy, [[polyuria]], seizures and coma. Other toxic effects of lithium include coarse tremor, [[muscle twitching]], [[convulsion]]s and [[renal failure]].<ref>Gelder, M., Mayou, R. and Geddes, J. 2005. Psychiatry. 3rd ed. New York: Oxford. pp249.</ref> People who survive a poisoning episode may develop persistent neurotoxicity. Several authors have described a "Syndrome of Irreversible Lithium-Effected Neurotoxicity" (SILENT), associated with episodes of acute lithium toxicity or long-term treatment within the appropriate dosage range. Symptoms are said to include [[Cerebellum|cerebellar]] dysfunction.<ref>{{cite journal|last=Adityanjee|coauthors=Munshi, Thampy|journal=Clinical Neuropharmacology|year=2005|volume=28|issue=1|pages=38-49|pmid=15714160}}</ref>
===Measurement in body fluids===
Lithium concentrations in whole blood, plasma, serum or urine may be measured using instrumental techniques as a guide to therapy, to confirm the diagnosis in potential poisoning victims or to assist in the forensic investigation in a case of fatal overdosage. Serum lithium concentrations are usually in the 0.5–1.3 mmol/l range in well-controlled patients, but may increase to 1.8–2.5 mmol/l in patients who accumulate the drug over time and to 3–10 mmol/l in victims of acute overdosage.<ref>{{cite journal|author=Amdisen A. |title=Clinical and serum level monitoring in lithium therapy and lithium intoxication|journal= J. Anal. Toxicol. |volume=2|pages=193–202|year=1978}}</ref><ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 851–854.</ref>
==References==
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{{DEFAULTSORT:Lithium Pharmacology}}
[[Category:Antipsychotics|*]]
[[Category:Lithium]]
[[Category:Mood stabilizers]]
[[Category:Biology and pharmacology of chemical elements]]