Citalopram Hydrobromide (Page 6 of 9)

Adverse Findings Observed in Short-Term, Placebo-Controlled Trials

Adverse Events Associated with Discontinuation of Treatment

Among 1,063 depressed patients who received citalopram at doses ranging from 10 to 80 mg/day in placebo-controlled trials of up to 6 weeks in duration, 16% discontinued treatment due to an adverse event, as compared to 8% of 446 patients receiving placebo. The adverse events associated with discontinuation and considered drug-related (i.e., associated with discontinuation in at least 1% of citalopram-treated patients at a rate at least twice that of placebo) are shown in TABLE 2. It should be noted that one patient can report more than one reason for discontinuation and be counted more than once in this table.

TABLE 2
Adverse Events Associated with Discontinuation of Treatment in Short-Term, Placebo-Controlled, Depression Trials
Percentage of Patients Discontinuing
Due to Adverse Event
Citalopram Placebo
(N=1,063) (N=446)
Body System/Adverse Event
General
Asthenia 1% <1%
Gastrointestinal Disorders
Nausea 4% 0%
Dry Mouth 1% <1%
Vomiting 1% 0%
Central and Peripheral
Nervous System Disorders
Dizziness 2% <1%
Psychiatric Disorders
Insomnia 3% 1%
Somnolence 2% 1%
Agitation 1% <1%

Adverse Events Occurring at an Incidence of 2% or More Among Citalopram-Treated Patients Table 3 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred among 1,063 depressed patients who received citalopram at doses ranging from 10 to 80 mg/day in placebo-controlled trials of up to 6 weeks in duration. Events included are those occurring in 2% or more of patients treated with citalopram and for which the incidence in patients treated with citalopram was greater than the incidence in placebo-treated patients.

The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.

The only commonly observed adverse event that occurred in citalopram patients with an incidence of 5% or greater and at least twice the incidence in placebo patients was ejaculation disorder (primarily ejaculatory delay) in male patients (see TABLE 3).

TABLE 3

*Events reported by at least 2% of patients treated with citalopram are reported, except for the following events which had an incidence on placebo citalopram: headache, asthenia, dizziness, constipation, palpitation, vision abnormal, sleep disorder, nervousness, pharyngitis, micturition disorder, back pain.

1 Denominator used was for females only (N=638 citalopram; N=252 placebo).

2 Primarily ejaculatory delay.

3 Denominator used was for males only (N=425 citalopram; N=194 placebo).

Treatment-Emergent Adverse Events:
Incidence in Placebo-Controlled Clinical Trials*
(Percentage of Patients Reporting Event)
Body System/Adverse Event Citalopram Placebo
(N=1,063) (N=446)
Autonomic Nervous System Disorders
Dry Mouth 20% 14%
Sweating Increased 11% 9%
Central & Peripheral Nervous System Disorders
Tremor 8% 6%
Gastrointestinal Disorders
Nausea 21% 14%
Diarrhea 8% 5%
Dyspepsia 5% 4%
Vomiting 4% 3%
Abdominal Pain 3% 2%
General
Fatigue 5% 3%
Fever 2% <1%
Musculoskeletal System Disorders
Arthralgia 2% 1%
Myalgia 2% 1%
Psychiatric Disorders
Somnolence 18% 10%
Insomnia 15% 14%
Anxiety 4% 3%
Anorexia 4% 2%
Agitation 3% 1%
Dysmenorrhea 1 3% 2%
Libido Decreased 2% <1%
Yawning 2% <1%
Respiratory System Disorders
Upper Respiratory Tract Infection 5% 4%
Rhinitis 5% 3%
Sinusitis 3% <1%
Urogenital
Ejaculation Disorder 2,3 6% 1%
Impotence 3 3% <1%

Dose Dependency of Adverse Events

The potential relationship between the dose of citalopram administered and the incidence of adverse events was examined in a fixed-dose study in depressed patients receiving placebo or citalopram 10, 20, 40, and 60 mg. Jonckheere’s trend test revealed a positive dose response (p<0.05) for the following adverse events: fatigue, impotence, insomnia, sweating increased, somnolence, and yawning.

Male and Female Sexual Dysfunction with SSRIs

Although changes in sexual desire, sexual performance, and sexual satisfaction often occur as manifestations of a psychiatric disorder, they may also be a consequence of pharmacologic treatment. In particular, some evidence suggests that SSRIs can cause such untoward sexual experiences.

Reliable estimates of the incidence and severity of untoward experiences involving sexual desire, performance, and satisfaction are difficult to obtain, however, in part because patients and physicians may be reluctant to discuss them. Accordingly, estimates of the incidence of untoward sexual experience and performance cited in product labeling, are likely to underestimate their actual incidence.

The table below displays the incidence of sexual side effects reported by at least 2% of patients taking citalopram in a pool of placebo-controlled clinical trials in patients with depression.

Treatment Citalopram Placebo
(425 males) (194 males)
Abnormal Ejaculation 6.1% 1%
(mostly ejaculatory delay) (males only) (males only)
Libido Decreased 3.8% <1%
(males only) (males only)
Impotence 2.8% <1%
(males only) (males only)

In female depressed patients receiving citalopram, the reported incidence of decreased libido and anorgasmia was 1.3% (n=638 females) and 1.1% (n=252 females), respectively.

There are no adequately designed studies examining sexual dysfunction with citalopram treatment.

Priapism has been reported with all SSRIs.

While it is difficult to know the precise risk of sexual dysfunction associated with the use of SSRIs, physicians should routinely inquire about such possible side effects.

Vital Sign Changes

Citalopram and placebo groups were compared with respect to (1) mean change from baseline in vital signs (pulse, systolic blood pressure, and diastolic blood pressure) and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses did not reveal any clinically important changes in vital signs associated with citalopram treatment. In addition, a comparison of supine and standing vital sign measures for citalopram and placebo treatments indicated that citalopram treatment is not associated with orthostatic changes.

Weight Changes

Patients treated with citalopram in controlled trials experienced a weight loss of about 0.5 kg compared to no change for placebo patients.

Laboratory Changes

Citalopram and placebo groups were compared with respect to (1) mean change from baseline in various serum chemistry, hematology, and urinalysis variables, and (2) the incidence of patients meeting criteria for potentially clinically significant changes from baseline in these variables. These analyses revealed no clinically important changes in laboratory test parameters associated with citalopram treatment.

ECG Changes

In a thorough QT study, citalopram was found to be associated with a dose-dependent increase in the QTc interval (see WARNINGS — QT-Prolongation and Torsade de Pointes).

Electrocardiograms from citalopram (N=802) and placebo (N=241) groups were compared with respect to outliers defined as subjects with QTc changes over 60 msec from baseline or absolute values over 500 msec post-dose, and subjects with heart rate increases to over 100 bpm or decreases to less than 50 bpm with a 25% change from baseline (tachycardic or bradycardic outliers, respectively). In the citalopram group 1.9% of the patients had a change from baseline in QTcF >60 msec compared to 1.2% of the patients in the placebo group. None of the patients in the placebo group had a post-dose QTcF >500 msec compared to 0.5% of the patients in the citalopram group. The incidence of tachycardic outliers was 0.5% in the citalopram group and 0.4% in the placebo group. The incidence of bradycardic outliers was 0.9% in the citalopram group and 0.4% in the placebo group.

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