Clomipramine Hydrochloride

Obsessive-Compulsive Disorder (OCD)

Among the drugs of choice for the management of OCD.69 289 293 296 297

Reduces but does not completely eliminate obsessions and compulsions.96 271 292 300

Panic Disorder

Has been used effectively for the management of panic disorder† with or without agoraphobia†.2 3 4 104 105 106 107 108 109 110 116 347

Major Depressive Disorder

Has been used effectively for the management of major depressive disorder†.2 3 254 255 256 257 258 259 260 267 277 278 282 288

Despite comparable efficacy,2 3 255 256 257 258 260 277 282 283 the adverse effect profile (e.g., anticholinergic effects) of clomipramine may limit its usefulness relative to other antidepressants (e.g., TCAs, SSRIs).2 257 258 277 282 283 288 289

Effective antidepressant when obsessive manifestations accompany episode of major depressive disorder.288

Chronic Pain

Has been used for the management of chronic pain† (e.g., central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, cancer pain) alone or as adjunct to conventional analgesics.2 3 52 111 112 113 114 115 118 119 120 121 122 123 124 125 343 344

Cataplexy and Associated Narcolepsy

Has been used for the symptomatic management of cataplexy† in a limited number of patients with cataplexy† and associated narcolepsy†.3 132 133 279

Autistic Disorder

Has been used for the management of repetitive and obsessive-compulsive behaviors and hyperactivity associated with autistic disorder†;134 135 141 285 286 does not treat core symptoms of autistic disorder.b

Trichotillomania

Has been used for the management of trichotillomania† (an urge to pull out one’s hair) in a limited number of patients with the disorder;3 136 137 138 139 relapse reported in some patients receiving long-term therapy.140

Onychophagia

Has been used for the management of severe onychophagia† (nail biting) without a history of OCD.142

Associated with relatively high dropout rate because of adverse effects and drug intolerance; not considered first-line therapy in most patients with onychophagia.142 341

Eating Disorders

Has been used for the management of anorexia nervosa† in a limited number of patients with the disorder.229 230 231

Initial therapeutic effects (e.g., improved eating behavior, weight gain) not sustained with long-term therapy (e.g., ≥8 weeks).229 230 231 234

Avoid use in underweight individuals and in those exhibiting suicidal ideation.288 341

Premature Ejaculation

Has been used for the management of premature ejaculation†.3 128 129 130 131

Premenstrual Syndrome

Has been used for the management of premenstrual syndrome†.261 262 263 264

General

• Allow at least 2 weeks to elapse between discontinuance of therapy with an MAO inhibitor and initiation of clomipramine and vice versa.1 Also allow at least 5 weeks to elapse when switching from fluoxetine.1

• Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments.d e f (See Worsening of Depression and Suicidality Risk under Cautions.)

• Sustained therapy may be required;2 4 33 78 80 81 82 148 341 use lowest effective dosage and monitor periodically for need for continued therapy.1 299

• Avoid abrupt discontinuance of therapy.1 2 78 148 301 To avoid withdrawal reactions, taper dosage gradually (e.g., over a period of approximately 2 weeks).1 2 78 148 301

Panic Disorder†

• Transient increase in the number and intensity of panic attacks may occur during initial therapy with the drug.4 104 105 106 288

Administration

Oral Administration

Administer orally; initially, in divided doses with meals to lessen adverse GI effects.1 After initial dosage titration, the total daily dose may be given once daily at bedtime1 2 4 271 to minimize adverse effects (e.g., sedation) during waking hours1 2 and enhance patient compliance.2

Also has been administered IM† or IV†, but a parenteral dosage form is not commercially available in the US.4 272

Dosage

Available as clomipramine hydrochloride; dosage is expressed in terms of the salt.1

Individualize dosage carefully according to individual requirements and response.1

Allow 2–3 weeks to elapse between any further dosage adjustments after the initial dosage titration period for achievement of steady-state plasma concentrations.1

Pediatric Patients

Children >10 years of age: initially, 25 mg daily.1 Gradually increase dosage, as tolerated, during the first 2 weeks of therapy up to a maximum of 3 mg/kg or 100 mg daily, whichever is lower.1 2 242 Titrate dosage carefully.1 If necessary, dosages may be increased gradually during the next several weeks up to a maximum of 3 mg/kg or 200 mg daily (whichever is lower).1 2 3 4 66 67

Optimum duration not established; 1 78 271 some clinicians recommend that therapy be continued in responding patients at the minimally effective dosage for at least 18 months before attempting to discontinue.1 271 299

Adults

Initially, 25 mg daily.1 Gradually increase dosage, as tolerated, during the first 2 weeks of therapy to approximately 100 mg daily.1 If necessary, dosages may be increased gradually during the next several weeks up to a maximum of 250 mg daily.1 2 3 4 66 67

Optimum duration not established; 1 78 271 some clinicians recommend that therapy be continued in responding patients at the minimally effective dosage for at least 18 months before attempting to discontinue.1 271 299

Usual dosage: ≤50 mg daily (range: 12.5–150 mg daily);2 4 104 105 106 107 108 110 116 272 patients with agoraphobia may require higher dosage.4 104 105 106

100–250 mg daily.2 272 277 278 288

100–250 mg daily.2 115 272 288

25–200 mg daily.132 133 272 279

Prescribing Limits

Pediatric Patients

Maximum 3 mg/kg or 200 mg daily, whichever is lower.1 2 3 4 66 67

Adults

Maximum 250 mg daily.1 2 3 4 66 67

Maximum 200 mg daily.2 4 104 105 106 107 108 110 116 272

Special Populations

Geriatric Patients

Manufacturer makes no specific recommendation for dosage adjustment1 41 240 but lower clomipramine hydrochloride dosages are recommended by some clinicians at least during initial therapy.2 4 272 282

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.1

Extensively metabolized in the liver by various CYP isoenzymes (e.g., CYP1A2,346 CYP2C,73 CYP2D6,72 73 CYP3A4).c

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP2D6 and/or 1A2: Potential pharmacokinetic interaction (increased plasma clomipramine concentrations).a Monitor plasma clomipramine concentrations whenever a CYP2D6 inhibitor is added or discontinued and adjust dosages as needed.a

Drugs Associated with Serotonin Syndrome

Potential pharmacologic (serotonin syndrome) interaction with serotonergic agents.1 175 302 303 Avoid such use whenever clinically possible.1 302 303

Drugs Affecting the Seizure Threshold

Use caution with concurrent administration of clomipramine and drugs (e.g., other antidepressants, antipsychotic agents) that lower the seizure threshold.1

Protein-bound Drugs

Potential for clomipramine to displace or to be displaced by other protein-bound drugs.1 Observe patients for adverse effects.1 2

Specific Drugs

• Risk of suicidality; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment.d e f FDA recommends providing written patient information (medication guide) explaining risks of suicidality each time the drug is dispensed.d e f

• Importance of informing patients about the risk of seizures associated with the drug.1

• Importance of discussing with patients the risk of serious injury to themselves or others resulting from sudden loss of consciousness (e.g., because of seizures) while engaged in certain complex and hazardous activities (e.g., operation of complex machinery, driving a motor vehicle, swimming, climbing).1

• Importance of cautioning patients about the use of alcohol, barbiturates, or other CNS depressants (see Interactions).1 243

• Importance of informing male patients about the relatively high incidence of sexual dysfunction associated with the drug.1 3 180

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name