Lithium interaction with other drugs

Jefferson JW, Greist JH, Baudhuin M. Lithium interactions with other drugs. J Clin Psychopharmacol 1981 1(3) 124—34. 

Lithium interacts with other drugs. Neurotoxicity has been reported in association with haloperidol and other antipsychotic drugs, most particularly when both are given in high doses for a prolonged period... 

Interactions with other drugs have been less closely studied, but anecdotal reports suggest that lithium, a drug used to stabilize mood in people with manic depression or bipolar disorder, increases the response to LSD. 

SSRIs can provoke 5HT neurotoxicity (the 5HT syndrome) through pharmacodynamic interactions with other drugs that also potentiate 5HT function. Often the ability of the interacting drug to facilitate 5HT function is well known, as is the case, for example, when SSRIs are combined with monoamine oxidase inhibitors or lithium. In other cases, however, the potential 5HT activity of the co-administered drug is not widely known. The ability of the antibiotic linezolid to inhibit MAO and thereby to cause 5HT neurotoxicity in combination with SSRIs has been noted previously (SEDA-27, 14), and further cases have now been reported. 

Antidepressants are considered to have additive effects, therefore combined use is not recommended. Inhibitors of serotonin reuptake by CNS neurons may interact with other drugs or circumstances which cause serotonin release. The enhancement of the serotonergic effects may produce a life-threatening serotonin syndrome. Drugs which can increase the serotonin level when taken in combination with SSRIs include TCAs, MAOIs, reversible inhibitors of monoamine oxidase, carbamazepine, lithium, or serotoneric substances. These drugs should not be coadministered with SSRIs and they may increase the risks of developing a serotonin syndrome. 

Phelan KM, Mosholder AD, Lu S. Lithium interaction with the cyclooxygenase 2 inhibitors rofecoxib and cele-coxib and other nonsteroidal anti-inflammatory drugs. J Clin Psychiatry 2003 64 1328-34. 

Ensuring that other drugs or treatments are not administered which may interact with the psychotropic drug under investigation (e.g. lithium, electroconvulsive therapy). 

Dmg interactions Drug interactions between Neupogen and other drugs have not been fully evaluated. Drugs that may potentiate the release of neutrophils from bone marrow, such as lithium, should be used with caution. 

As noted earlier, lithium is contraindicated in patients with unstable congestive heart failure or the sick sinus node syndrome ( 307, 328). In older patients or those with prior cardiac histories, a pretreatment ECG should be obtained. Except for the potential adverse interactions with diuretics, the concomitant use of other cardiac drugs is generally safe. Because verapamil may lower serum levels of lithium, however, more careful monitoring may be required to assure continued therapeutic effects (329). Some data also indicate that verapamil may predispose to lithium neurotoxicity. Conversely, increased lithium levels leading to toxicity has occurred with methyidopa and enalapril. When antihypertensive therapy is necessary, b-blockers are a reasonable choice when lithium is coadministered. 

LITHIUM OTHER-VENLAFAXINE Possible risk of serotonin syndrome Additive effect Be aware of the possibility of serotonin syndrome. Also need to monitor lithium levels with appropriate dose adjustments during co-administration >- For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome... 

As can be expected, many drugs that interfere with renal function also influence lithium excretion. This and other drug interactions are listed in Table 1. 

Lithium is also known to interact in a variety of ways with different classes of diuretic drugs. Thiazide diuretics increase serum lithium concentration by increasing reabsorption of lithium, along with that of sodium, in the proximal tubule. With potassium-sparing diuretics, conflicting results have been reported. Increased serum lithium concentrations may be seen after amiloride. However, the loop diuretic furosemide safely can be combined with lithium with no reduction in renal lithium clearance or consequent increase in serum lithium concentration (191, 192). Other diuretics, for example, carbonic anhydrase inhibitor and xanthine derivatives, decrease serum... 

Klonopin (clonazepam) A conunon medication used as a mood stabilizer often prescribed for the following reasons inadequate response or intolerance to antipsychotics or lithium, manic symptoms, rapid cycling of the condition, EEC abnormalities, and head trauma. The most common side effects are difficulty with balance and drowsiness. Behavioral and emotional side effects include irritability, excitement, increased anger and aggression, trouble sleeping or nightmares, and memory loss. The most serious side effect is the interaction effect if this medication is combined with alcohol or other drugs, which can result in sleepiness, unconsciousness, and death. 

Care needs to be taken when combining naproxen with other medications. Known adverse drug interactions can occur with aspirin, methotrexate, ACE inhibitors (for high blood pressure), furosemide, lithium, and warfarin (a blood thinner). An overdose of naproxen may cause dizziness, drowsiness, and gastrointestinal problems. High blood pressure, kidney failure, and coma may occur, but are rare. 

A mentally retarded patient had occasional hypothermic episodes (below 35°C) while taking lithium and diazepam, but not while taking either drug alone. After taking lithium 1 g and diazepam 30 mg daily for 17 days, the patient s temperature fell from 35.4 to 32°C over 2 hours, and he became comatose with reduced reflexes, dilafed pupils, a systolic blood pressure of 40 to 60 mmHg, a pulse rate of 40 and no piloerecfor response. The reasons for fhis reacfion are nof known. This is an isolated case and fhere-fore concurrenf use need nof be avoided, buf be alert for any evidence of hypothermia. There seems to be no evidence of this adverse interaction with any of the other benzodiazepines. 

One UK manufacturer warns that drugs affecting electrolyte balance, such as corticosteroids, may alter lithium excretion and should therefore be avoided, but other manufaeturers do not appear to mention this potential interaction. An early study in rats reported increased lithium clearance with methylprednisolone. The available evidence is insufficient to recommend routine monitoring. However, it may be prudent to consider monitoring lithium effects in patients with renal impairment, or other conditions pre-disposing to lithium toxicity, taking levels if early symptoms suggest a potential problem. 

In this age of sophisticated drug design and biotechnolcgy, the simple lithium ion is still the most effective treatment of this destructive psy-cholcgical disorder. Remarkably, in spite of intensive research, scientists still do not fully understand the biochemical action of lithium that leads to its therapeutic effects. Because of its similarity to Na, Li" is incorporated into blood plasma, where it can affect the behavior of nerve and muscle cells. Because Li has a smaller radius than Na (Figure 7.7), the way Li interacts with molecules in human cells is different from the way Na interacts with the molecules. Other studies indicate that Li alters the function of certain neurotransmitters, which might lead to its effectiveness as an antipsychotic drug. 

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