Minds On Meds

Mental Health Medications

Antidepressants

Wellbutrin, Page 4

Wellbutrin (bupropion hydrochloride) is an antidepressant of the aminoketone class and is indicated for the treatment of major depressive disorder. While not approved for smoking cessation treatment, bupropion under the name Zyban is approved for this use. Effectiveness of Wellbutrin in long-term use, that is, for more than 6 weeks, has not been systematically evaluated in controlled trials.

Labor and Delivery

The effect of WELLBUTRIN on labor and delivery in humans is unknown.

Nursing Mothers

Like many other drugs, bupropion and its metabolites are secreted in human milk. Because of the potential for serious adverse reactions in nursing infants from WELLBUTRIN, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established (see BOX WARNING and WARNINGS: Clinical Worsening and Suicide Risk in Treating Psychiatric Disorders). Anyone considering the use of WELLBUTRIN in a child or adolescent must balance the potential risks with the clinical need.

Geriatric Use

Of the approximately 6,000 patients who participated in clinical trials with bupropion sustained-release tablets (depression and smoking cessation studies), 275 were 65 and over and 47 were 75 and over. In addition, several hundred patients 65 and over participated in clinical trials using the immediate-release formulation of bupropion (depression studies). No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

A single-dose pharmacokinetic study demonstrated that the disposition of bupropion and its metabolites in elderly subjects was similar to that of younger subjects; however, another pharmacokinetic study, single and multiple dose, has suggested that the elderly are at increased risk for accumulation of bupropion and its metabolites (see CLINICAL PHARMACOLOGY).

Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. The risk of toxic reaction to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see PRECAUTIONS: Renal Impairment and DOSAGE AND ADMINISTRATION).

ADVERSE REACTIONS

(See also WARNINGS and PRECAUTIONS.)

Adverse events commonly encountered in patients treated with WELLBUTRIN are agitation, dry mouth, insomnia, headache/migraine, nausea/vomiting, constipation, and tremor.

Adverse events were sufficiently troublesome to cause discontinuation of treatment with WELLBUTRIN in approximately 10% of the 2,400 patients and volunteers who participated in clinical trials during the product’s initial development. The more common events causing discontinuation include neuropsychiatric disturbances (3.0%), primarily agitation and abnormalities in mental status; gastrointestinal disturbances (2.1%), primarily nausea and vomiting; neurological disturbances (1.7%), primarily seizures, headaches, and sleep disturbances; and dermatologic problems (1.4%), primarily rashes. It is important to note, however, that many of these events occurred at doses that exceed the recommended daily dose.

Accurate estimates of the incidence of adverse events associated with the use of any drug are difficult to obtain. Estimates are influenced by drug dose, detection technique, setting, physician judgments, etc. Consequently, Table 2 is presented solely to indicate the relative frequency of adverse events reported in representative controlled clinical studies conducted to evaluate the safety and efficacy of WELLBUTRIN under relatively similar conditions of daily dosage (300 to 600 mg), setting, and duration (3 to 4 weeks). The figures cited cannot be used to predict precisely the incidence of untoward events in the course of usual medical practice where patient characteristics and other factors must differ from those which prevailed in the clinical trials. These incidence figures also cannot be compared with those obtained from other clinical studies involving related drug products as each group of drug trials is conducted under a different set of conditions.

Finally, it is important to emphasize that the tabulation does not reflect the relative severity and/or clinical importance of the events. A better perspective on the serious adverse events associated with the use of WELLBUTRIN is provided in WARNINGS and PRECAUTIONS.

Table 2. Treatment-Emergent Adverse Experience Incidence in Placebo-Controlled Clinical Trialsa (Percent of Patients Reporting)

Adverse Experience

WELLBUTRIN Patients

(n = 323)

Placebo Patients

(n = 185)

Cardiovascular

Cardiac arrhythmias

5.3

4.3

Dizziness

22.3

16.2

Hypertension

4.3

1.6

Hypotension

2.5

2.2

Palpitations

3.7

2.2

Syncope

1.2

0.5

Tachycardia

10.8

8.6

Dermatologic

Pruritus

2.2

0.0

Rash

8.0

6.5

Gastrointestinal

Anorexia

18.3

18.4

Appetite increase

3.7

2.2

Constipation

26.0

17.3

Diarrhea

6.8

8.6

Dyspepsia

3.1

2.2

Nausea/vomiting

22.9

18.9

Weight gain

13.6

22.7

Weight loss

23.2

23.2

Genitourinary

Impotence

3.4

3.1

Menstrual complaints

4.7

1.1

Urinary frequency

2.5

2.2

Urinary retention

1.9

2.2

Musculoskeletal

Arthritis

3.1

2.7

Neurological

Akathisia

1.5

1.1

Akinesia/bradykinesia

8.0

8.6

Cutaneous temperature disturbance

1.9

1.6

Dry mouth

27.6

18.4

Excessive sweating

22.3

14.6

Headache/migraine

25.7

22.2

Impaired sleep quality

4.0

1.6

Increased salivary flow

3.4

3.8

Insomnia

18.6

15.7

Muscle spasms

1.9

3.2

Pseudoparkinsonism

1.5

1.6

Sedation

19.8

19.5

Sensory disturbance

4.0

3.2

Tremor

21.1

7.6

Neuropsychiatric

Agitation

31.9

22.2

Anxiety

3.1

1.1

Confusion

8.4

4.9

Decreased libido

3.1

1.6

Delusions

1.2

1.1

Disturbed concentration

3.1

3.8

Euphoria

1.2

0.5

Hostility

5.6

3.8

Nonspecific

Fatigue

5.0

8.6

Fever/chills

1.2

0.5

Respiratory

Upper respiratory complaints

5.0

11.4

Special Senses

Auditory disturbance

5.3

3.2

Blurred vision

14.6

10.3

Gustatory disturbance

3.1

1.1

a Events reported by at least 1% of patients receiving WELLBUTRIN are included.