Amitriptyline and chlordiazepoxide

You should not use this medicine if you have recently had a heart attack.

Do not use this medicine if you have used an MAO inhibitor in the past 14 days, such as isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, or tranylcypromine.

Some young people have thoughts about suicide when first taking an antidepressant. Stay alert to changes in your mood or symptoms. Report any new or worsening symptoms to your doctor.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Amitriptyline and chlordiazepoxide may be habit-forming. Never share this medicine with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it. Selling or giving away this medicine is against the law.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

It may take up to 4 weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve.

If you need surgery, tell the surgeon ahead of time that you are using amitriptyline and chlordiazepoxide. You may need to stop using the medicine for a short time.

Do not stop using amitriptyline and chlordiazepoxide suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using amitriptyline and chlordiazepoxide.

Your doctor will need to check your progress while you are using amitriptyline and chlordiazepoxide. If you use this medicine long-term, you may need frequent medical tests.

Store at room temperature away from moisture and heat.

Keep track of the amount of medicine used from each new bottle. Amitriptyline and chlordiazepoxide is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

• It is used to treat low mood (depression).
• It is used to treat anxiety.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of low mood (depression), thoughts of killing yourself, nervousness, emotional ups and downs, thinking that is not normal, anxiety, or lack of interest in life.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Change in how you act.
• Hallucinations (seeing or hearing things that are not there).
• Chest pain or pressure or a fast heartbeat.
• A heartbeat that does not feel normal.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Very bad dizziness or passing out.
• Feeling confused.
• Shakiness.
• Trouble controlling body movements, twitching, change in balance, trouble swallowing or speaking.
• Fever or chills.
• Sore throat.
• Very bad headache.
• Not able to pass urine.
• Very bad belly pain.
• Any unexplained bruising or bleeding.
• Feeling very tired or weak.

Depression: Treatment of moderate-to-severe depression associated with moderate to severe anxiety

Hypersensitivity to benzodiazepines, tricyclic antidepressants, or any component of the formulation; coadministration with or within 14 days of MAO inhibitors; acute recovery phase following myocardial infarction (MI)

See individual agents.

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Amitriptyline and chlordiazepoxide combination is not FDA approved for use in children.

• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Patients treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia.

• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, increased intraocular pressure (IOP), narrow-angle glaucoma, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. The degree of anticholinergic blockade produced by amitriptyline is very high relative to other antidepressants.

• Fractures: Bone fractures have been associated with antidepressant treatment. Consider the possibility of a fragility fracture if an antidepressant-treated patient presents with unexplained bone pain, point tenderness, swelling, or bruising (Rabenda, 2013; Rizzoli, 2012).

• Hematologic effects: TCAs may rarely cause bone marrow suppression; monitor for any signs of infection and obtain CBC if symptoms (eg, fever, sore throat) evident.

• Ocular effects: May cause mild pupillary dilation which in susceptible individuals can lead to an episode of narrow-angle glaucoma. Consider evaluating patients who have not had an iridectomy for narrow-angle glaucoma risk factors.

• Orthostatic hypotension: May cause orthostatic hypotension (risk is very high relative to other antidepressants); use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia). Therapy is relatively contraindicated in patients with symptomatic hypotension.

• Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients.

• Sedation: Both agents may cause sedation, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). The degree of sedation is very high relative to other antidepressants.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with a history of cardiovascular disease (including previous MI, stroke, tachycardia, or conduction abnormalities); the risk conduction abnormalities with amitriptyline is high relative to other antidepressants. Heart block may be precipitated in patients with preexisting conduction system disease and use is relatively contraindicated in patients with conduction abnormalities.

• Diabetes: Use amitriptyline with caution in patients with diabetes mellitus; may alter glucose regulation.

• Drug abuse: Use chlordiazepoxide with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use.

• Hepatic impairment: Use both agents with caution in patients with hepatic impairment.

• Impaired gag reflex: Use chlordiazepoxide with caution in patients with an impaired gag reflex.

• Mania/hypomania: May worsen psychosis in some patients or precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Patients presenting with depressive symptoms should be screened for bipolar disorder. This combination is not FDA approved for the treatment of bipolar depression.

• Porphyria: Use chlordiazepoxide with caution in patients with porphyria.

• Renal impairment: Use both agents with caution in patients with renal impairment.

• Respiratory disease: Use chlordiazepoxide with caution in patients with respiratory disease.

• Seizure disorder: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Debilitated patients: Use chlordiazepoxide with caution in debilitated patients; active metabolites with extended half-lives may lead to delayed accumulation and adverse effects.

• Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury.

Other warnings/precautions:

• Appropriate use: Chlordiazepoxide does not have analgesic, antidepressant, or antipsychotic properties.

• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, lightheadedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA, 2010; Fava, 2006; Haddad, 2001; Shelton, 2001; Warner, 2006).

• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.

• Surgery: Recommended by the manufacturer to discontinue prior to elective surgery; risks exist for drug interactions with anesthesia and for cardiac arrhythmias. However, definitive drug interactions have not been widely reported in the literature and continuation of tricyclic antidepressants is generally recommended as long as precautions are taken to reduce the significance of any adverse events that may occur. Norepinephrine should be considered the vasopressor of choice for TCA-related hypotension (Pass, 2004). Therapy should not be abruptly discontinued in patients receiving high doses for prolonged periods. Chronic use of chlordiazepoxide may increase the perioperative benzodiazepine dose needed to achieve desired effect.

• Tolerance: Chlordiazepoxide is a long half-life benzodiazepine. Duration of action after a single dose is determined by redistribution rather than metabolism. Tolerance does not develop to the anxiolytic effects (Vinkers, 2012).

• Withdrawal: Rebound or withdrawal symptoms may occur following abrupt discontinuation of chlordiazepoxide or large decreases in dose. Use caution when reducing dose or withdrawing therapy; decrease slowly and monitor for withdrawal symptoms. Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy.

Evaluate mental status, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased); anxiety, social functioning, mania, panic attacks or other unusual changes in behavior; respiratory status; heart rate, blood pressure and ECG in older adults and patients with preexisting cardiac disease; blood glucose; weight and BMI; periodic liver function tests and CBC (prolonged therapy)

Data not available