Citalopram dosing

Citalopram and fluoxetine also have been studied in panic disorder (Michelson et al. 1998 Wade et al. 1997). Citalopram was compared with clomipramine. At the most effective citalopram dose (20-30 mg/day), approximately 58% of patients were panic-free compared with 50% of patients receiving clomipramine and 32% of placebo patients. All rating scales suggested that 20 or 30 mg/day of citalopram was more effective than 40 or 60 mg/day of citalopram. Finally, data support the efficacy of fluoxetine in panic disorder. In a study comparing 10 and 20 mg/day of fluoxetine and placebo, fluoxetine treatment, particularly the 20-mg daily dose, was associated with more improvement than placebo across multiple measures, including functional impairment. 

Preliminary studies in 5 patients found that their mean plasma clozapine levels were unchanged by citalopram. Another study in 8 patients found similar results. However, a patient who was stable taking clozapine developed sedation, hypersalivation and confusion shortly after he started to take citalopram 40 mg daily. When total clozapine serum levels were measured they were found to be 1097 nanograms/mL. The citalopram dose was reduced to 20 mg daily, the symptoms resolved over the following 2 weeks, and the total clozapine level dropped to 792 nanograms/mL. ... 

Drug overdose Seizures are a recognized, albeit uncommon, complication of overdose with a number of SSRI antidepressants, but the susceptibility factors have not been elucidated. Qf 241 patients who presented with overdose of citalopram, 7.5% had generalized seizures [33 ]. Co-ingested venlafaxine or tricyclic antidepressants increased the risk substantially (QR = 15). In the absence of co-ingested drugs, the minimum citalopram dose associated with seizures was 400 mg, with an increase in the odds ratio for seizures of 1.1 for every 100 mg increment in citalopram dose. 

It is perhaps not surprising that, even after taking into account pharmacokinetic differences between these drugs, the therapeutic doses of the SSRIs do not parallel their Ki for inhibition of 5-HT reuptake. For instance, citalopram is about a thousand times more selective than fluoxetine for inhibition of 5-HT uptake, and yet their clinically effective doses are similar. In short, not only is their selectivity for the 5-HT transporter in vitro a poor predictor of their efficacy in vivo but it has to be questioned whether any of these compounds actually work by blocking 5-HT uptake alone. 

Since the neurotoxic effects of drugs such as parachloroamphetamine on serotonin neurons can be prevented by serotonin uptake blockers (Ross 1976 Sanders-Bush and Steranka 1978). the possibility that serotonin uptake carrier protein was likewise involved in the neurotoxic effects of MDMA was investigated. As shown in figure 4, pretreatment of rats with the seleetive serotonin uptake blocker citalopram (10 ml/kg), prior to each injection of 10 mg/kg MDMA, resulted in nearly complete protection against the neurotoxic effects of MDMA. Citalopram-pretreated rats exhibited only a 15 pereent decrease in serotonin uptake sites. No significant alterations in the eontent of serotonin and 5-HIAA were observed following MDMA treatment, in eomparison with 60 to 80 percent reductions in the serotonergie parameters observed in rats treated with an identical dose of MDMA alone. 

SSRIs Citalopram 10-30 mg fluoxetine 10-20 mg fluvoxamine 50 mg paroxetine 10-30 sertraline 25-150 mg all agents are given by mouth daily and can be dosed continuously or during the luteal phase only26 Sexual dysfunction (reduced libido, anorgasmia), insomnia sedation, hypersomnia, nausea, diarrhea... 

SSRIs are theorized to reduce the frequency of hot flashes by increasing serotonin in the central nervous system and by decreasing LH. Of the SSRIs, citalopram, paroxetine, and sertraline all have been studied and have demonstrated a reduction in hot flashes while treating other symptomatic complaints such as depression and anxiety.33 Venlafaxine, which blocks the reuptake of serotonin and norepinephrine, has demonstrated a reduction in hot flashes primarily in the oncology population.34 Overall, these antidepressant medications offer a reasonable option for women who are unwilling or cannot take hormonal therapies, particularly those who suffer from depression or anxiety. These agents should be prescribed at the lowest effective dose to treat symptoms and may be titrated based on individual response. 

A small, flexible dose study of citalopram (dosage range = 10-40 mg/day) in 14 Hispanic and 6 non-Hispanic (non-White) depressed HIV-positive patients conducted in Miami also showed no differences in response rate or effective dose between ethnicities (Currier etal., 2004). In addition, Hispanic patients did not have a significantly higher attrition rate compared to non-Hispanics. 

Another study with citalopram evaluated its efficacy in the treatment of social anxiety disorder along with co-morbid major depression (Schneier etal., 2003). The outpatients (n= 21) were predominantly Hispanic (76%) and from New York. Response rates for the intent-to-treat sample were 66.7% for social anxiety disorder and 76.2% for major depression. Only one subject was known to have withdrawn secondary to severe side effects. The mean dose of the medication was 37.6 mg/day and there was no placebo control. The depressive symptoms tended to improve... 

The SSRIs, with the possible exception of citalopram and sertraline, may have a nonlinear pattern of drug accumulation with chronic dosing. 

Both enantiomers and the racemate of l-(3,4-dichlorophenyl)-3-azabicyclo [3.1.0]hexane, 27a-c, have been reported to be in development. The racemate, DOV 216,303, inhibits the reuptake of NE, 5-HT and DA with IC50 values of 20, 14 and 78 nM, respectively [85]. DOV 216,303 is active in tests predictive of antidepressant activity, including the mouse FST (minimum effective dose = lOmg/kg), reversal of tetrabenazine-induced ptosis and locomotor depression. DOV 216,303 was also reported to be well tolerated in phase I clinical trials [85,86], In a phase II study designed to explore safety and tolerability in depressed individuals, patients received either DOV 216,303 (50 mg, b.i.d.) or citalopram (20 mg, b.i.d.) for two weeks [85]. It was found that the side effect profile was not remarkably different between the two treatment groups. In addition, time-dependent reductions in Hamilton Depression Scores (HAM-D) were similar for both groups. 

If the patient has missed one or several doses there might be a need to overcompensate for the missing doses and to restore steady-state levels fast, but general rules are hard to give. Nowadays, this information is often available in the package leaflet for each medication. The information is also available on EMEA home page (EMEA 2008). Fore many medications there is no recommendation. For some medications like simvastatin, citalopram and atenolol the advice is not to compensate for missing doses. 

SSRls. SSRI antidepressants have also received considerable scrutiny in the treatment of OCD. Fluoxetine, fluvoxamine, paroxetine, and sertraline are all approved by the FDA for the treatment of OCD. Current studies suggest that each of these medications is more effective for OCD when administered at the higher end of the therapeutic dose range, that is, fluoxetine 60-80 mg/day, fluvoxamine 200-300 mg/ day, paroxetine 40-60 mg/day, and sertraline 150-200 mg/day. No controlled studies are yet available regarding the use of citalopram or escitalopram for OCD. Refer to Chapter 3 for more information regarding SSRl antidepressants. 

Discontinuation of treatment Symptoms associated with discontinuation of citalopram and other SSRIs and SNRIs have been reported. Monitor patients for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. 

Renal function impairment No dose adjustment of citalopram, fluoxetine, or fluvoxamine in renally impaired patients is routinely necessary. 

In subjects with hepatic impairment, clearance of racemic citalopram was decreased and plasma concentrations were increased. The recommended dose of escitalopram in hepatically impaired patients is 10 mg/day. 

Elderly Clearance of fluvoxamine is decreased by about 50% in elderly patients. A lower starting dose of paroxetine is recommended. Sertraline plasma clearance may be lower. In 2 pharmacokinetic studies, citalopram AUC was increased by 23% and 30%, respectively, in elderly subjects as compared with younger subjects, and its half-life was increased by 30% and 50%, respectively. In 2 pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in elderly subjects as compared with young subjects and C ax was unchanged. 

Time to reach peak plasma level decreased from 8 hours post-dosing to 5.5 hours. Food does not appear to affect systemic bioavailability of fluoxetine although it may delay absorption. Fluvoxamine and citalopram bioavailability is not affected by food. Thus, fluoxetine, fluvoxamine, and citalopram may be given with or without food. 

Citalopram (Celexa) [Antidepressant/SSRI] WARNING Closely monitor for worsening depression or emergence of suicidality, particularly in pts <24 y Uses Depression Action SSRI Dose Initial 20 mg/d, may t to 40 mg/d X in elderly hqjatic/renal insuff Caution [C, +/-] Hx of mania, Szs pts at risk for suicide Contra MAOI or w/in 14 d of MAOI use Disp Tabs, cap, soln SE Somnolence, insomnia, anxiety, xerostomia, diaphoresis, sexual dysfxn Notes May cause X Na /SIADH Interactions t Effects W/ azole antifungals, cimetidine, Li, macrolides, EtOH t effects OF BBs, carbamazepine, CNS drugs, warfarin X effects W/ carbamaz ine X effects OF phenytoin may cause fatal Rxn W/ MAOIs EMS Use caution w/ CNS depressants, may need a reduced dose concurrent EtOH... 

These drugs increase synaptic serotonin by selectively blocking the serotonin reuptake transporter. In preclinical and human studies acute doses tend to be anxiogenic (Bell and Nutt 1998) but chronic administration has anxiolytic effects, possibly due to downregulation of presynaptic autoreceptors (Blier et al. 1990). There are five SSRIs widely available citalopram, fluoxetine, fluvoxam-ine, paroxetine and sertraline. Escitalopram, the S-enantiomer of citalopram. 

SSRIs—fluvoxamine, fluoxetine, and paroxetine, more than sertraline and citalopram Inhibition of metabolism at CYP2D6 isoenzyme TCA toxicity due to up to 10-fold increase in TCA levels with coadministration Lower TCA dose Baumann, 1996... 

In children and adolescents, the half-times for antidepressants such as paroxetine, sertraline, and citalopram are between 14 and 16 hours (Clein and Riddle, 1995 Findling et ah, 1999 (Axelson et ak, 2000 a,b). This suggests that these medications, particular when prescribed at lower doses, need to be administered twice a day. Otherwise, children and adolescents can expe-... 

Clinical pharmacology. A bicyclic isobenzofurane derivative, citalopram is nearly completely absorbed after oral administration, with 80% available after first-pass metabolism. Eighty-three percent of that absorbed is protein bound, and peak plasma concentrations are reached in 3 hours (range 1-6 hours] (Milne and Goa 1991]. Even though citalopram s half-life is 33-35 hours, steady-state levels are achieved only after 1-2 weeks, reflecting the longer half-life of its metabolites demethylcitalopram (half-life = 49 hours] and didemethylcitalopram (half-life = 102 hours] (P. Baumann 1992]. Mainly eliminated by hepatic metabolism, citalopram s biotransformation is not fully understood as the parent compound, and its two metabolites account for only 45%-50% of the dose in urine (Van Harten 1993]. 

A trial comparing 10, 20, 40 and 60mg/day of citalopram and placebo in the treatment of moderate-to-severe major depression. This study showed that the 40 and 60 mg dose arms had significantly superior efficacy in comparison with placebo (Feighner and Overo, 1999). 

Feighner, J.P., Overo, K. Multicenter, placebo-controlled, fixed-dose study of citalopram in moderate-to-severe depression. J. Clin. Psychiatry 60 824-830, 1999. 

Following a single oral dose of citalopram, peak blood levels occur at about four hours. 

All of the SSRIs also show a flat dose-response curve, meaning that there is usually no advantage to increasing the dose above that which is the usually effective minimum dose. Of interest, the four SSRIs marketed as antidepressants in the United States at their usual effective therapeutic dose (i.e., 40 mg per day for citalopram, 20 mg per day for paroxetine and fluoxetine, and 50 mg per day for sertraline) produce comparable effects on either plasma serotonin levels or the serotonin uptake pump in platelets (25). These results are consistent with the conclusion that serotonin uptake inhibition is the mechanism responsible for the antidepressant efficacy of these agents. 

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