Citalopram adverse effects

SSRIs are widely used for treatment of depression, as well as, for example, panic disorders and obsessive—compulsive disorder. These dmgs are well recognized as clinically effective antidepressants having an improved side-effect profile as compared to the TCAs and irreversible MAO inhibitors. Indeed, these dmgs lack the anticholinergic, cardiovascular, and sedative effects characteristic of TCAs. Their main adverse effects include nervousness /anxiety, nausea, diarrhea or constipation, insomnia, tremor, dizziness, headache, and sexual dysfunction. The most commonly prescribed SSRIs for depression are fluoxetine (31), fluvoxamine (32), sertraline (52), citalopram (53), and paroxetine (54). SSRIs together represent about one-fifth of total worldwide antidepressant unit sales. 

Fluvoxamine, fluoxetine, and paroxetine have nonlinear pharmacokinetics, which means that dose increases lead to disproportionately greater increases in plasma drug levels (25). In contrast, citalopram and sertraline have linear pharmacokinetics. For these reasons, dose increases with fluvoxamine, fluoxetine, and paroxetine can lead to greater than proportional increases in concentration-dependent effects such as serotonin-mediated adverse effects (e.g., nausea) and inhibition of specific CYP enzymes. 

In 1988, fluoxetine became the first SSRI marketed in the United States. Since then, sertraline (1992), paroxetine (1993), fluvoxamine (1994) and citalopram (1998) have been marketed. Their widespread acceptance has added substantially to the patient-years of experience with these medications. Thus, the confidence in our knowledge of the adverse effect profile of these drugs in the general population and in special populations (e.g., the elderly, the medically ill) has grown substantially over the past decade. 

Fluoxetine is a potential drug of abuse.136 Overdose with sertraline causes suicidal tendencies, whereas citalopram causes fatal reactions such as cardiac dysfunction.137 The adverse effects could be treated with stomach wash, administration of activated charcoal, dialysis, and hemoperfusion. 

Gastrointestinal adverse effects are one of the major disadvantages of SSRIs. The most common is nausea, and the incidence is said to be 20% or more for paroxetine (45,46), sertraline (47), fluvoxamine (5), fluoxetine (48), and citalopram (10,49). Although nausea can lead to drug withdrawal, it usually disappears after a few weeks. Other gastrointestinal symptoms that occur commonly with fluoxetine and sertraline are loose stools and diarrhea (47,48,50), while constipation has been more often reported with fluvoxamine (5) and paroxetine (45,46). 

Their most frequent adverse events (nausea, somnolence, dry mouth, increased sweating) are mainly transient and mostly mild to moderate (3). In terms of adverse effects escitalopram appears to be equivalent to citalopram. For example, in placebo-controlled trials, escitalopram produced unwanted effects typical of the SSRI class, including nausea (15%), ejaculation disorders (9%), insomnia (9%), diarrhea (8%), somnolence (7%), dry mouth (6%), and dizziness (6%). 

The fact that withdrawal of citalopram led to rapid resolution of the diplopia suggests that it was due to the citalopram, but the mechanism of this rare adverse effect is unclear. 

Gastrointestinal adverse effects are one of the major disadvantages of SSRIs. The most common is nausea, and the incidence is said to be 20% or more for citalopram (19,20). 

However, in a 39-year-old man with a schizoaffective disorder, citalopram 40 mg/day appeared to increase plasma clozapine concentrations and increased adverse effects (33). The adverse effects settled within 2 weeks of a reduction in citalopram dosage to 20 mg/day, with a corresponding 25% fall in clozapine concentrations. It is possible that at higher doses, citalopram can increase clozapine concentrations, perhaps through inhibition of CYP1A2 or CYP3A4. 

SSRIs ATOMOXETINE t plasma concentrations and risk of adverse effects (abdominal pain, vomiting, nausea, fatigue, irritability) Atomoxetine is a selective norepinephrine reuptake inhibitor, t plasma concentrations due to inhibition of CYP2D6 by fluoxetine and paroxetine (potent), fluvoxamine and sertraline (less potent) and escitalopram and citalopram (weak) Avoid concurrent use. The interaction is usually severe with fluoxetine and paroxetine... 

Both theophyUine and citalopram are metabolized by CYP1A2. In an open, multiple-dose study in 13 healthy nonsmoking volunteers, steady-state citalopram therapy had no significant effect on theophylhne metabolism. The authors suggested that dosage adjustment of theophyUine may not be necessary in patients taking concurrent citalopram (52). The most frequent treatment-related adverse effects were fatigue and nausea. 

Citalopram Animal reproductive studies have revealed adverse effects on fetal and postnatal development at a dose higher than the human therapeutic dose. 

The SSRIs (paroxetine, fluoxetine, sertraline, fluvoxamine, citalopram) and SNRI (ven-lafaxine) have an impressive side-effect profile, and this has contributed to their widespread use. Possible adverse effects include nausea, insomnia, and agitation, but these are generally manageable and diminish over time. More significant is the association of the SSRIs with sexual dysfunction, in both men and women. These effects are longer lasting, and can occur in up to 40% of patients (79). A withdrawal syndrome has also been observed with the SSRIs, characterized by dizziness, headache, and irritability upon abrupt discontinuation. This is much less serious than that observed with benzodiazepines. 

The SSRIs include fluoxetine, citalopram, sertraline, paroxetine, es-citalopram, and fluvoxamine. The SSRIs have a low affinity for his-taminic, a i-adrenergic, and muscarinic receptors, and therefore produce fewer anticholinergic and cardiovascular adverse effects than the TCAs, and are not associated with weight gain. The most... 

Patients treated with paroxetine or sertraline showed improvement in anxiety and avoidance symptoms and a decrease in disability. Daily doses up to 60 mg of paroxetine and 200 mg of sertraline were well tolerated, and emergent adverse effects were similar to those of depression trials (e.g., nausea, sexual dysfunction, sweating, and somnolence). The onset of effect was delayed 4 to 8 weeks, and maximum benefit was often not observed until 12 weeks or longer. Sertraline is also effective in disabled patients suffering from the marked to severe form of generalized SAD. Limited data suggest that citalopram, escitalopram, and fluvoxamine are also effective in treating SAD. Fluoxetine was not effective in SAD. ... 

ANS adverse effects and cardiotoxic potential than tricyclics. Tox CNS stimulation, sexual dysfunction, seizures in overdose, serotonin syndrome. Other SSRIs citalopram, paroxetine, sertraline. 

B. Selective serotonin reuptake inhibitors. Studies have shown that citalopram and serotonin in doses of 20 0 mg/day are effective in the treatment of painful diabetic neuropathy but not as efficacious as tricyclic antidepressants [29], However, they do have less adverse effects, and accordingly they are recommended to be given to patients that do not tolerate tricyclic antidepressants. Upper gastric bleeding is a reported adverse effects and concomitant use of NSAID increases this risk. 

The study of ecstasy with citalopram was primarily undertaken to find out how eestasy works, but on the basis of these results and animal studies it seems likely that patients already taking citalopram may not be able to get as high on usual doses of ecstasy, and some adverse effects may also be redueed. Furthermore, if the proposed mechanism of interaction is correct, the same is also likely to be true if they are taking any other SSRI and some cases have been reported. However, be aware of possible pharmaeokinetie interaetions with some SSRIs that are potent CYP2D6 inhibitors (e.g. fluoxetine, paroxetine), which may increase ecstasy levels. There is also a risk of increased serotonergic activity and there have been a few reports of interaetions involving other sympathomimetics and SSRIs or related drugs, see Phentermine + Fluoxetine , p.205. 

On the whole significant interactions between the antipsychotics and SSRIs appear rare (although see thioridazine, below). The combination can be useful and so the isolated cases of extrapyramidal adverse effects should not prevent concurrent use. However, if extrapyramidal effects become troublesome bear this interaction in mind as a possible cause. The significance of the rise in haloperidol levels caused by fluoxetine and fluvoxamine is unclear, be aware that haloperidol adverse effects may be increased in some patients and consider reducing the haloperidol dose if problems occur. The rise in perphenazine levels caused by paroxetine seems to result in a greater number of more serious adverse effects and so consideration should be given to reducing the dose of perphenazine if paroxetine is started. Citalopram may be a suitable alternative as it does not appear to affect perphenazine levels. 

The manufacturers say that fluoxetine 60 mg daily for 8 days caused an increase of 16% in olanzapine maximum serum levels and a 16% decrease in clearance. These differences were considered to be too small to necessitate dosage adjustments. Similar results were found in a published study. A case report describes a patient who had been taking fluoxetine 80 mg daily for several weeks with no adverse effects who developed the serotonin syndrome within 3 weeks of starting to take olanzapine 5 mg daily. His symptoms resolved after discontinuing the fluoxetine, and he was later able to tolerate a 20 mg daily dose of fluoxetine and olanzapine with no further adverse effects. The serotonin syndrome has also been reported in a patient taking olanzapine, citalopram and lithium, see Olanzapine + Lithium , p.756. 

Although the evidence is limited, it appears that nefazodone can cause a marked rise in ciclosporin levels, with an increase in adverse effects. Alternative antidepressants should probably be used, or concurrent therapy very well monitored. Similar caution would seem prudent with fluvoxamine, and possibly fluoxetine. Citalopram, and sertraline do not appear to alter ciclosporin levels and may therefore be suitable alternatives. Serotonin syndrome is a rare adverse effect, usually associated with the use of more than one serotonergic drug (see The serotonin syndrome , (p.9)). 

No pharmacokinetic changes were seen in one study in 8 healthy subjects when lithium 30 mmol/day (as lithium sulfate 1.98 g daily) was added to citalopram 40 mg daily. Another study, in 24 patients who had previously not responded to citalopram alone, found that the concurrent use ofeitalo-pram 40 or 60 mg and lithium carbonate 800 mg daily was effeetive and did not increase adverse effects. Even so, the manufacturers of eitalopram suggest that concurrent use should be undertaken with caution, as they are aware of reports of enhanced serotonergic effects when lithium and SSRIs are used together. 

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