Lithium SSRIs

Which one of the following should not be taken with combined oral contraceptives (paracetamol/rifampicin/vitamin D/lithium/SSRIs)... 

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 T and l 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 i the reuptake of 5- HT these are considered to t 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... 

Abstinence maintenance Antabuse, naltrexone, lithium, SSRIs ... 

Antipsychotic drugs Benzodiazepines Lithium SSRIs Stimulants TCAs... 

There is a decreased effectiveness of fluoxetine in patients who smoke cigarettes during administration of die drug. Fluoxetine is not administered witii lithium because this combination can increase lithium levels. The SSRIs are not administered witii herbal preparations containing St. Jbhn s wort because tiiere is an increased risk for severe reactions. 

Optimize the dose of mood stabilizing medication(s) before adding on lithium, lamotrigine, or antidepressant (e.g., bupropion or an SSRI) if psychotic features are present, add on an antipsychotic ECT used for severe or treatment-resistant depressive episodes or for psychosis or catatonia... 

Consider augmentation ) (non-SSRI antidepressant, lithium, thyroid hormone,... 

Add lithium to a standard antidepressant (e.g. an SSRI) maintaining the plasma lithium concentration at 0.4-0.6mmol/l. This is a well-established method with approximately 50% of the patients responding. However, the plasma lithium concentration must be monitored. 

Treatment of choice - mood stabilizer with or without an antidepressant (e.g. lithium, valproate, carbamazepine, lamotrigine). Antidepressants include an SSRI, venlafaxine, mirtazepine as possibilities but few controlled trials to substantiate choice. 

Drugs that may affect SSRIs Drugs that may affect SSRIs include azole antifungals, barbiturates, carbamazepine, cimetidine, cyproheptadine, lithium, macrolides,... 

Drugs that may be affected by SSRIs Drugs that may be affected by SSRIs include alcohol, benzodiazepines, beta blockers, buspirone, carbamazepine, cisapride, clozapine, cyclosporine, diltiazem, digoxin, haloperidol, hydantoins, lithium, methadone, mexiletine, nonsedating antihistamines, NSAIDs, olanzapine, phenothiazines, phenytoin, pimozide, procyclidine, ritonavir, ropivacaine, sumatriptan, sulfonylureas, sympathomimetics, tacrine, theophylline, tolbutamide, tricyclic antidepressants, and warfarin. 

Dmg-induced serotonin syndrome is generally mild and resolves when the offending drugs are stopped. However, it can be severe and deaths have occurred. A large number of drugs have been implicated including tricyclic antidepressants, monoamine oxidase inhibitors (MAOIs), selective serotonin re-uptake inhibitors (SSRIs), pethidine, lithium, and dextromethorphan. The most severe type of reaction has occurred with the combination of selective serotonin re-uptake inhibitors and monoamine oxidase inhibitors. Both non-selective MAOIs such as phenelzine and selective MAOIs such as moclobemide and selegiline have been implicated. 

The TCAs, SSRIs, and lithium have been found to be efficacious for the prevention of depressive recurrences in adults (APA, 2000). However, given the noted advantages of the SSRIs and their efficacy in the acute treatment of MDD and dysthymia, this group is considered the first-choice medication for Intervention. 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

The nature of the aromatic substituents is apparently not critical for SSRI activity, as indicated by the structure of duloxetine (23-5), where one ring is replaced by thiophene and the other by naphthalene. The synthesis starts as above by the formation of the Mannich base (23-1) from 1-acetyl thiophene with formaldehyde and dimethyl-amine. Treatment of that intermediate with the complex from lithium aluminum hydride and the 2R,3S entantiomer of dimethylamino-l,2-diphenyl-3-methyl-butane-2-ol gives the S isomer (23-2) in high enantiomeric excess. Treatment of the aUcoxide from (23-2) and sodium hydride with 1-fluoronaphthalene leads to the displacement of halogen and thus the formation of ether (23-2). The surplus methyl group is then removed by yet another variant of the von Braun reaction that avoids the use of a base for saponifying the intermediate urethane. Thus, reaction of (23-3) with trichloroethyl formate leads to the A -demethylated chlorinated urethane (23-4). Treatment of that intermediate with zinc leads to a loss of the carbamate and the formation of the free secondary amine duloxetine (23-5) [23]. 

Although initial reports concluded that low-dose lithium could augment the effect in patients partially responsive to an SSRI ( 373), subsequent reports have been less encouraging (374, 375). Furthermore, there is an increase in bothersome adverse effects when lithium is added to SSRI therapy (376). Both of these factors plus the need for TDM when using lithium has caused this approach to fall from favor in recent years. 

SSRIs reduce dopamine cell firing in the substantia nigra through their effects on serotonin input to this nucleus. The net result is that they can cause generally mild extrapyramidal side effects (EPS) (500). The most common are restlessness and tremors. The same mechanism is probably responsible for their interaction with other agents that affect central motor systems. Thus, the SSRIs can potentiate the tremor seen with lithium, as well as EPS caused by antipsychotics, bupropion, and psychostimulants (376, 500). 

Nonsteroidal anti-inflammatory drugs (SSRIs given) [NE] Reduced renal lithium excretion (except sulindac and salicylates). 

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