chapter
Antidepressants
Pages 47

Uncertain; NSAIDs possibly ↓ renal clearance of lithium

Monitor lithium levels closely

LITHIUM ANTIARRHYTHMICS – AMIODARONE

1. Rare risk of ventricular arrythmias, particularly torsades de pointes 2. Risk of hypothyroidism

1. Additive effect; lithium rarely causes Q-T prolongation 2. Additive effect; both drugs can cause hypothyroidism

1. Manufacturers of amiodarone recommend avoiding co-administration 2. If co-administration thought to be necessary, watch for symptoms/ signs of hypothyroidism; check TFTs every 3-6 months

LITHIUM ANTIBIOTICS – METRONIDAZOLE

≠ plasma concentrations of lithium with risk of toxicity

Uncertain Monitor clinically and by measuring blood lithium levels for lithium toxicity

LITHIUM ANTIDEPRESSANTS

LITHIUM SSRIs Lithium may enhance the pharmacologic effects of SSRIs and potentiate the risk of serotonin syndrome. Excessive somnolence has been reported with fluvoxamine. However, there are reports of both ≠ and ↓ plasma concentrations of lithium. There are reports of lithium toxicity and of serotonergic effects

Lithium is a direct stimulant of 5-HT receptors, while SSRIs ↓ the reuptake of 5-HT; these are considered to ≠ the effects of serotonin in the brain. Seizures are a neurotoxic effect of lithium and could occur even with plasma lithium concentrations within the normal range. SSRIs and lithium may have additive effects to cause seizures

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

N ER

V O

U SSY

STEM D

R U

G S

A N

TID EPR

ESSA N

TS157

NERVOUS SYSTEM DRUGS ANTIDEPRESSANTS Lithium

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

LITHIUM ANTIEPILEPTICS – CARBAMAZEPINE, PHENYTOIN

≠ risk of neurotoxicity Uncertain; this may occur with normal lithium blood levels

Warn patients and carers to watch for drowsiness, ataxia and tremor

LITHIUM ANTIHYPERTENSIVES AND HEART FAILURE DRUGS

LITHIUM ACE INHIBITORS ≠ efficacy of lithium ≠ plasma concentrations of lithium (up to one-third) due to ↓ renal excretion

Watch for lithium toxicity. Monitor lithium levels

LITHIUM ANGIOTENSIN II RECEPTOR ANTAGONISTS

Risk of lithium toxicity ↓ excretion of lithium possibly due to ↓ renal tubular reabsorption of sodium in the proximal tubule

Watch for lithium toxicity. Monitor lithium levels

LITHIUM CENTRALLY ACTING ANTIHYPERTENSIVES

1. Methyldopa may reduce the effect of antidepressants 2. Case reports of lithium toxicity when co-ingested with methyldopa. It was noted that lithium levels were in the therapeutic range

1. Methyldopa can cause depression 2. Uncertain at present

1. Methyldopa should be avoided in patients with depression 2. Avoid co-administration if possible; if not, watch closely for clinical features of toxicity and do not rely on lithium levels

N ER

V O

U SSY

STEM D

R U

G S

A N

TID EPR

ESSA N

TS

Mechanism Precautions

PHENOTHIAZINES, SULPIRIDE

effects and of neurotoxicity

Uncertain Watch for development of these symptoms

LITHIUM SERTINDOLE ≠ risk of ventricular arrhythmias Uncertain Avoid concomitant use LITHIUM ANTIVIRALS –

ACICLOVIR/VALACICLOVIR ≠ lithium levels with risk of toxicity Possible ↓ renal excretion Ensure adequate hydration, monitor

lithium levels if intravenous aciclovir or4 g/day valaciclovir required

LITHIUM BETA-BLOCKERS Report of episode of ≠ lithium levels in an elderly patient after starting low-dose propanolol. However, propanolol is often used to treat lithium-induced tremor without problems

Mechanism uncertain at present, but propanolol seems to reduce lithium clearance

Monitor lithium levels when starting propanolol therapy in elderly patients

LITHIUM BRONCHODILATORS – THEOPHYLLINE

↓ plasma levels of lithium, with risk of therapeutic failure

Theophylline ≠ renal clearance of lithium

May need to ≠ dose of lithium by 60%

LITHIUM CALCIUM CHANNEL BLOCKERS

Small number of cases of neurotoxicity when co-administered with diltiazem or verapamil

Uncertain, but thought to be due to additive effect on neurotransmission

Monitor closely for side-effects

LITHIUM DIURETICS

LITHIUM ACETAZOLAMIDE ↓ plasma concentrations of lithium, with risk of inadequate therapeutic effect

≠ renal elimination of lithium Monitor clinically and by measuring blood lithium levels to ensure adequate therapeutic efficacy

LITHIUM LOOP DIURETICS, POTASSIUM-SPARING DIURETICS, ALDOSTERONE ANTAGONISTS, THIAZIDES

≠ plasma concentrations of lithium, with risk of toxic effects

↓ renal excretion of lithium Monitor clinically and by measuring blood lithium levels for lithium toxicity. Loop diuretics are safer than thiazides

N ER

V O

U SSY

STEM D

R U

G S

A N

TID EPR

ESSA N

TS159

NERVOUS SYSTEM DRUGS ANTIDEPRESSANTS Monoamine oxidase inhibitors

Uncertain Monitor intraoperative muscle relaxation closely; may need ≠ doses of muscle relaxants

LITHIUM BACLOFEN Enhancement of hyperkinesias associated with lithium

Uncertain Consider alternative skeletal muscle relaxant

LITHIUM PARASYMPATHOMIMETICS ↓ efficacy of neostigmine and pyridostigmine

Uncertain Watch for poor response to these parasympathomimetics and ≠ dose accordingly

LITHIUM SODIUM BICARBONATE ↓ plasma concentrations of lithium with risk of lack of therapeutic effect

Due to ≠ renal excretion of lithium Monitor clinically and by measuring blood lithium levels to ensure adequate therapeutic efficacy

MONOAMINE OXIDASE INHIBITORS

MAOIs ALCOHOL Additive depression of CNS ranging from drowsiness to coma and respiratory depression.