indication

Lithium is used as a mood stabilizer, and is used for treatment of depression and mania. It is often used in bipolar disorder treatment.

pharmacology

Although lithium has been used for over 50 years in treatment of bipolar disorder, the mechanism of action is still unknown. Lithium's therapeutic action may be due to a number of effects, ranging from inhibition of enzymes such as glycogen synthase kinase 3, inositol phosphatases, or modulation of glutamate receptors.

mechanism of action

The precise mechanism of action of Li+ as a mood-stabilizing agent is currently unknown. It is possible that Li+ produces its effects by interacting with the transport of monovalent or divalent cations in neurons. An increasing number of scientists have come to the conclusion that the excitatory neurotransmitter glutamate is the key factor in understanding how lithium works. Lithium has been shown to change the inward and outward currents of glutamate receptors (especially GluR3), without a shift in reversal potential. Lithium has been found to exert a dual effect on glutamate receptors, acting to keep the amount of glutamate active between cells at a stable, healthy level, neither too much nor too little. It is postulated that too much glutamate in the space between neurons causes mania, and too little, depression. Another mechanism by which lithium might help to regulate mood include the non-competitive inhibition of an enzyme called inositol monophosphatase. Alternately lithium's action may be enhanced through the deactivation of the GSK-3B enzyme. The regulation of GSK-3B by lithium may affect the circadian clock. GSK-3 is known for phosphorylating and thus inactivating glycogen synthase. GSK-3B has also been implicated in the control of cellular response to damaged DNA. GSK-3 normally phosphorylates beta catenin, which leads to beta catenin degratation. When GSK-3 is inhibited, beta catenin increases and transgenic mice with overexpression of beta catenin express similar behaviour to mice treated with lithium. These results suggest that increase of beta catenin may be a possible pathway for the therapeutic action of lithium.

drug interactions

Aminophylline: Theophylline decreases serum levels of lithium

Benazepril: The ACE inhibitor increases serum levels of lithium

Bendroflumethiazide: The thiazide diuretic, bendroflumethiazide, may increase serum levels of lithium.

Benzthiazide: The thiazide diuretic, benzthiazide, may increase serum levels of lithium.

Caffeine: Caffeine decreases serum levels of lithium

Candesartan: The ARB increases serum levels of lithium

Captopril: The ACE inhibitor increases serum levels of lithium

Celecoxib: The COX-2 inhibitor increases serum levels of lithium

Chlorothiazide: The thiazide diuretic, chlorothiazide, may increase serum levels of lithium.

Chlorthalidone: The thiazide diuretic, chlorthalidone, may increase serum levels of lithium.

Cilazapril: The ACE inhibitor increases serum levels of lithium

Citric Acid: The urine alkalizer decreases the effect of lithium

Cyclothiazide: The thiazide diuretic, cyclothiazide, may increase serum levels of lithium.

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Diclofenac: The NSAID, diclofenac, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.

Diflunisal: The NSAID, diflunisal, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.

Dyphylline: Theophylline decreases serum levels of lithium

Enalapril: The ACE inhibitor increases serum levels of lithium

Eplerenone: Eplerenone increases serum levels of lithium

Eprosartan: The ARB increases serum levels of lithium

Etoricoxib: Etoricoxib increases serum levels of lithium

Fluoxetine: The SSRI, fluoxetine, increases serum levels of lithium.

Fluvoxamine: The SSRI, fluvoxamine, increases serum levels of lithium.

Forasartan: The ARB increases serum levels of lithium

Fosinopril: The ACE inhibitor increases serum levels of lithium

Haloperidol: Possible extrapyramidal effects and neurotoxicity with this combination

Hydrochlorothiazide: The thiazide diuretic, hydrochlorothiazide, may increase serum levels of lithium.

Hydroflumethiazide: The thiazide diuretic, hydroflumethiazide, may increase serum levels of lithium.

Ibuprofen: The NSAID, ibuprofen, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.

Indapamide: The thiazide diuretic, indapamide, may increase serum levels of lithium.

Indomethacin: The NSAID, indomethacin, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.

Irbesartan: The ARB increases serum levels of lithium

Ketoprofen: The NSAID, ketoprofen, may increase the serum concentration of lithium by decreasing its renal clearance. Consider a dose reduction in lithium upon initiation of ketoprofen therapy. Monitor for changes in the therapeutic and adverse effects of lithium if ketoprofen is initiated, discontinued or does changed.

Ketorolac: The NSAID, ketorolac, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.

Lisinopril: The ACE inhibitor increases serum levels of lithium

Losartan: Losartan increases serum levels of lithium

Lumiracoxib: The COX-2 inhibitor increases serum levels of lithium

Mefenamic acid: The NSAID, mefenamic acid, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.

Meloxicam: Meloxicam increases serum levels of lithium

Methyclothiazide: The thiazide diuretic, methyclothiazide, may increase serum levels of lithium.

Methyldopa: Methyldopa may increase the adverse effects of lithium without affecting lithium serum levels. Monitor for signs and symptoms of lithium toxicity during concomitant therapy.

Metolazone: The thiazide diuretic, metolazone, may increase serum levels of lithium.

Metronidazole: Metronidazole increases the effect and toxicity of lithium

Moexipril: The ACE inhibitor increases serum levels of lithium

Naproxen: The NSAID, naproxen, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.

Oxtriphylline: Theophylline decreases serum levels of lithium

Perindopril: The ACE inhibitor increases serum levels of lithium

Phenylbutazone: The NSAID, phenylbutazone, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.

Piroxicam: The NSAID, piroxicam, may decrease the renal excretion of lithium. Increased risk of lithium toxicity.

Polythiazide: The thiazide diuretic, polythiazide, may increase serum levels of lithium.

Potassium: The urine alkalizer decreases the effect of lithium

Quinapril: The ACE inhibitor increases serum levels of lithium

Quinethazone: The thiazide diuretic, quinethazone, may increase serum levels of lithium.

Ramipril: The ACE inhibitor increases serum levels of lithium

Rofecoxib: The COX-2 inhibitor increases serum levels of lithium

Saprisartan: The ARB increases serum levels of lithium

Sibutramine: Possible serotoninergic syndrome with this combination

Sodium bicarbonate: The urine alkalizer decreases the effect of lithium

Spirapril: The ACE inhibitor increases serum levels of lithium

Sumatriptan: Possible serotoninergic syndrome with this combination

Tasosartan: The ARB increases serum levels of lithium

Telmisartan: Telmisartan may increase serum Lithium concentrations. Monitor serum Lithium levels during concomitant therapy to avoid Lithium toxicity.

Tenoxicam: Tenoxicam may increase the serum concentration of Lithium. A dose adjustment of Lithium may be required. Monitor for changes in Lithium therapeutic and adverse effects if Tenoxicam is initiated, discontinued or dose changed.

Theophylline: Theophylline decreases serum levels of lithium

Tiaprofenic acid: Tiaprofenic acid may increase the therapeutic/adverse effects of Lithium by increasing Lithium serum concentrations. Monitor for changes in the therapeutic/adverse effects of Lithium if Tiaprofenic acid is initiated, discontinued or dose changed.

Tobramycin: Increased risk of nephrotoxicity

Tolmetin: Tolmetin may increase the risk of Lithium toxicity by decreasing the renal elminiation of Lithium. A dose adjustment of Lithium may be required. Monitor for changes in Lithium therapeutic and adverse effects if Tolmetin is initiated, discontinued or dose changed.

Topiramate: Topiramate could modify lithium levels

Trandolapril: Trandolapril may increase the serum concentration of Lithium increasing the risk of Lithium toxicity. Monitor for changes in Lithium serum concentrations, toxicity and efficacy if Trandolapril is initiated, discontinued or dose changed.

Tranylcypromine: Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Trichlormethiazide: Trichlormethiazide may increase the serum concentration of Lithium by decreasing Lithium excretion. Monitor for changes in the therapeutic/adverse effects of Lithium if Trichlorthiazide is initiated, discontinued or dose changed.

Trimipramine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Valdecoxib: The COX-2 inhibitor increases serum levels of lithium

Valsartan: Valsartan may increase serum lithium concentrations. Monitor serum lithium levels during concomitant therapy to avoid lithium toxicity.

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Verapamil: Signs of lithium toxicity

Zolmitriptan: Use of two serotonin modulators, such as zolmitriptan and lithium, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.