Definition

Clozapine is an antipsychotic drug used to alleviate the symptoms and signs of schizophrenia—a form of severe mental illness— which is characterized by loss of contact with reality, hallucinations, delusions, and unusual behavior. In the United States, the drug is also known by the brand name Clozaril.

Purpose

Clozapine is principally used to reduce the signs and symptoms of severe schizophrenic illness. The drug is intended for use in patients with severe schizophrenia who have not responded to any other antipsychotic drug. Clozapine is also used in patients with severe schizophrenia when other antipsychotic medications have caused intolerable side effects.

Description

Clozapine is considered an atypical antipsychotic drug. Atypical antipsychotics differ from typical antipsychotics in their effectiveness in schizophrenia and their profile of side effects. Clozapine may reduce the signs and symptoms of schizophrenia in a large proportion of treatment-resistant schizophrenic patients who do not respond to typical antipsychotics. Moreover, the drug is less likely than typical antipsychotics to cause tardive dyskinesia and other extrapyramidal side effects. Tardive dyskinesia is a syndrome of involuntary, uncoordinated movements that may not disappear or may only partially improve after the drug is stopped. Tardive dyskinesia involves involuntary movements of the tongue, jaw, mouth or face or other groups of skeletal muscles. The incidence of tardive dyskinesia increases with increasing age and with increasing dosage. It may also appear after use of the antipsychotic has stopped. Women are at greater risk than men for developing tardive dyskinesia. There is no known effective treatment for this syndrome, although gradual (but rarely complete) improvement may occur over a long period.

Clozapine was the first atypical antipsychotic drug to be developed. In the late 1980s, clozapine was tested in severely ill schizophrenic patients who had been treated with a typical antipsychotic drug but had not shown much improvement. A significant proportion of these patients improved as a result of treatment with clozapine.

The superiority of clozapine in treatment-resistant patients is considered an important advance, but the drug is not without problems. Clozapine is generally considered the most toxic of the antipsychotic drugs. It causes agranulocytosis, a life-threatening depletion of white blood cells, in 1-2% of patients. It also causes epileptic seizures and adverse effects on the heart and blood pressure more frequently than other antipsychotic medicines. Clozapine is usually reserved for the most severely ill schizophrenic patients who have not responded to other treatments. Other atypical antipsychotic drugs have been developed in recent years, and they are considered safer to use than clozapine.

The mechanisms of action of antipsychotic drugs are not completely understood. The effect of clozapine is believed to be related to its actions in blocking neurotransmission due to the neurotransmitters dopamine and serotonin in a region of the brain called the limbic system, which is involved with emotions and motivation. The actions of clozapine may target the limbic system more specifically than those of typical antipsychotic drugs.

Clozapine is available as Clozaril, the only brand, as 25- and 100-mg tablets.

Recommended dosage

The usual dosage of clozapine is 300–600 mg per day; however, some patients may require daily dosages of up to 900 mg. To minimize side effects, the initial dose of clozapine is 12.5 mg (one-half tablet) twice a day, and the dose is increased by 25–50 mg each day, until the dose reaches 300–450 mg per day. The daily dosage of the drug is then determined based on the individual patient’s response, but increases should not exceed 100 mg once or twice a week.

Precautions

Clozapine may cause agranulocytosis, a life-threatening depletion of white blood cells. The blood cells affected by clozapine defend the body against infections by bacteria and other microorganisms, and patients with agranulocytosis are subject to severe infections. Clozapine treatment is reserved for the most severely ill schizophrenic patients who have not responded to other treatments. Clozapine is available only through a distribution system that assures close monitoring of white blood cells. Patients must have white blood cell counts determined before starting treatment, once every week for the first six months, once every other week after that, and once a week for the first month after clozapine treatment is stopped.

Clozapine may cause epileptic seizures in about 5% of patients. The frequency of seizures goes up as the dose of the drug is increased. Patients who experience seizures on clozapine should usually have the drug discontinued or the dose reduced. Neuroleptic malignant syndrome (NMS), a dangerous condition with high fever, muscular rigidity, rapid pulse, sweating, and altered mental state, may occur with all antipsychotic medications, including clozapine. NMS requires immediate medical treatment.

Clozapine frequently causes sedation and may interfere with driving and other tasks requiring alertness. The drug may increase the effects of alcohol and sedatives. Clozapine may cause low blood pressure and sudden drops in blood pressure on standing up, which may cause dizziness or fainting. Elevated heart rate may occur in 25% of patients; this effect may be a serious risk for patients with heart disease. Clozapine-induced fever, unrelated to any illness, may occur. The fever usually subsides within a few days, but it may require stopping the drug.

The safety and effectiveness of clozapine in children under 16 years old have not been established. Elderly patients may be particularly sensitive to sedation, low blood pressure, and other side effects. The drug should be used with caution in older patients. Clozapine should be used in pregnant women only when strictly necessary. The drug has not been adequately studied in pregnancy. In animal studies, however, clozapine has not produced harmful effects on the fetus. Clozapine may be secreted in breast milk, and breast-feeding may not be advisable.

Side effects

Clozapine may cause many side effects. The following side effects are grouped by the body system affected:

• Cardiovascular: decreases of blood pressure, especially on arising from a seated or lying position, which may cause dizziness or fainting; rapid heart rate, changes in heart rhythm and electrocardiogram.
• Nervous system: sedation, increased seizure tendency.
• Digestive system: increased appetite, excessive salivation, nausea, constipation, abnormal liver tests, elevated blood sugar.
• Autonomic: blurred vision, exacerbation of glaucoma, dry mouth, nasal congestion, decreased sweating; difficulty urinating, particularly in men with enlarged prostate.
• Skin: rashes.
• Body as a whole: weight gain, fever.

Interactions

Clozapine may interact with many other drugs. Patients should inform their physicians about all other drugs they are taking before starting treatment. Because of the risk of agranulocytosis, clozapine should not be given along with medications that suppress production of blood cells.

Clozapine may intensify the effects of drugs causing sedation, including alcohol, barbiturates, narcotic pain medications, minor tranquilizers, and antihistamines. Similarly, clozapine may cause excessive reductions of blood pressure in patients taking other medicines that lower blood pressure. Clozapine may also intensify side effects of drugs that cause blurred vision, dry mouth, diminished sweating in hot weather, and constipation. Many other antipsychotics and antidepressants cause such side effects.

Clozapine may potentiate (increase) the effects of other medications that also lower seizure threshold (make it more likely to have seizure), such as steroid drugs, the asthma medication theophylline, and many other psychiatric drugs. Patients with epilepsy may require adjustment in their dosage of anti-seizure medications. Lithium may increase the risk of seizures and other nervous system adverse effects when given with clozapine.

Certain drugs that are eliminated by the liver may interfere with the elimination of clozapine from the body, causing higher blood levels and increased side effects. Conversely, clozapine may interfere with the elimination of other drugs that are eliminated by the liver. Antidepressants that affect brain serotonin levels may increase blood levels of clozapine, possibly causing increased side effects.

Definition

Clorazepate is a medication that belongs to a family of drugs called benzodiazepines—a group of pharmacologically active compounds used to produce a calming effect by relieving anxiety and tension. In the United States, clorazepate is sold under brand names Tranxene and Gen-XENE.

Purpose

Clorazepate is used for the treatment of anxiety and alcohol withdrawal. Moreover, clorazepate is an adjunct in the management of partial seizures.

Description

Clorazepate binds to different sites in the brain, causing them to shift into a state that is less excitable. It is very effective in treating anxiety and anxiety disorders. Moreover, anxiety associated with undergoing surgical procedures is controlled with clorazepate. Clorazepate alone is not efficacious in treating seizures; however, if used along with other standard seizure medications, such as phenobarbital, primidone, phenytoin, carbamazepine, and valproic acid, better seizure control may be achieved. Convulsions and anxiety associated with alcohol withdrawal are controlled with clorazepate.

Clorazepate is available in two different formulations. Clorazepate tablets come in 3.75-, 7.5-, and 15-mg doses, while slow-release tablets, administered once daily, are available in 11.25- and 22.5-mg strengths. Capsules are available in 3.75-, 7.5-, and 15-mg strengths.

Recommended dosage

If used for anxiety, the dose of clorazepate usually ranges anywhere from 15 mg to 60 mg daily in divided dose intervals. Usually, however, the average dose is 30 mg daily given in two to four doses. If slow-release formulation is used, the dose of either 11.25 mg or 22.5 mg is usually administered at bedtime. Slow-release products should not be used to initiate therapy.

Doses of clorazepate for the management of seizures differ in adult and pediatric populations. Patients who are nine to 12 years of age should be started on 3.75–7.5 mg twice daily. This dose should be increased by no more than 3.75 mg weekly. The maximum dose per day is 60 mg administered in two to three divided doses. Children older than 12 and adults should receive 7.5 mg two to three times daily. This can be increased to a higher dose by adding 7.5 mg at weekly intervals. The total daily dose should not exceed 90 mg daily administered in two to three doses. In patients undergoing alcohol withdrawal, the first dose is 30 mg. Treatment is continued with 15 mg two to four times daily for the maximum dose of 90 mg in one day. Once maximum dose is achieved, the dose is gradually decreased over subsequent days.

Precautions

Pregnant women should not take clorazepate. Patients who have narrow-angle glaucoma should not take clorazepate, as this may worsen their condition. Clorazepate should not be used in patients younger than nine years of age.

If depression coexists with anxiety, clorazepate should be used with caution as suicidal tendencies may be present. (One of the side effects with this medication is depression; if a patient has an underlying problem with depression, that problem can be exacerbated with clorazepate.) Patients should be cautioned against engaging in hazardous occupations requiring mental alertness, since clorazepate causes drowsiness and dizziness. Abrupt discontinuation of clorazepate has been associated with withdrawal symptoms and seizures. Hence, doses of clorazepate should be slowly decreased in patients who have been taking clorazepate continuously over several weeks. Other withdrawal symptoms may include nervousness, insomnia, irritability, diarrhea, and muscle aches. The doses for elderly patients, as well as patients with liver or kidney problems, may need to be decreased.

Side effects

The most common side effects include drowsiness, dizziness, and confusion. There are a few reports about behavioral changes associated with the use of clorazepate and they include rage, depression, irritability, and aggression.

Other side effects include vision disturbances—such as blurred and double vision—decreased libido, nausea, vomiting, either decreased or increased appetite, and diarrhea or constipation. In a few cases, clorazepate has been associated with liver toxicity where patients developed jaundice or fever. It is also known to cause a rash.

Interactions

Simultaneous use of clorazepate and dong quai, a Chinese herb, has been associated with excessive muscle relaxation and central nervous system depression. Other herbs that should not be used with clorazepate include ginkgo biloba and kava kava.

Omeprazole, a medication used to treat heartburn, should not be used together with clorazepate. Medicines to treat disorders associated with increased acid secretions—such as ranitidine, sucralfate, and pantoprazole— are not contraindicated with clorazepate. Valerian, an herb used as a sleep aid, binds to the same receptors in the brain as clorazepate; thus, the desired effects of clorazepate may not be seen in patients taking it and valerian at the same time.

Clorazepate may increase the effects of other drugs that cause drowsiness,. These drugs include antihistamines (such as Benadryl), sedatives (usually used to treat insomnia), pain relievers, anxiety and seizure medicines, and muscle relaxants. Alcohol combined with clorazepate also causes excessive drowsiness.

Definition

Clonidine belongs to a class of drugs called central alpha-adrenergic agonists. In the United States, clonidine tablets are sold under the brand name Catapres and clonidine skin patches are sold under the brand name Catapres-TTS. The tablets are also available generically. There is also an injectable form that is administered directly into the spinal cord for the treatment of postoperative pain.

Purpose

Clonidine tablets and patches are approved by the United States Food and Drug Administration (FDA) for the treatment of high blood pressure. However, clonidine has been found to be useful in the treatment of alcohol, opiate, and nicotine withdrawal syndromes, attention-deficit/hyperactivity disorder (ADHD), and Tourette’s syndrome, one of the tic disorders.

Description

Clonidine was synthesized in 1960s and was initially tested as a nasal decongestant. In the United States, clonidine was first used to treat hypertension although it has also been investigated for treatment of different neuropsychiatric disorders. Clonidine works on specific nerve cells in the brain that are responsible for lowering blood pressure, slowing heart rate, and decreasing the body’s reaction to the withdrawal of chemicals like alcohol, opiates, cocaine, and nicotine. Because of this, clonidine is often used to treat the symptoms of drug, alcohol, and nicotine withdrawal.

Clonidine is beneficial in opiate withdrawal because it treats symptoms that are commonly associated with that condition (watery eyes and nose, diarrhea, irritability). For this condition, clonidine is often used alone. For the treatment of alcohol withdrawal, clonidine is usually combined with benzodiazepine tranquilizers such as Librium, Valium, Xanax, or Ativan.

Several studies of treatment for smoking cessation showed patients treated with clonidine had decreased nicotine craving. Clonidine skin patches appear to be more effective than tablets in this condition. Both dermal patches and tablets are effective in the treatment of Tourette’s syndrome and ADHD.

Clonidine tablets are available in 0.1-mg, 0.2-mg, and 0.3-mg strengths. Clonidine skin patches are available in 0.1-mg, 0.2-mg, and 0.3-mg per day patches. Each patch lasts seven days.

Recommended dosage

Dosages of 0.4–0.6 mg have been used for the treatment of alcohol withdrawal. Total daily dosage for the treatment of opiate withdrawal range between 0.5 and 1.4 mg, depending on the stage as well as the severity of withdrawal symptoms. If the clonidine patch is used to treat nicotine withdrawal symptoms, dosages that deliver 0.1–.2 mg daily are used. For oral therapy (tablets), a total dosage of 0.2–0.4 mg daily is taken in divided doses.

Pediatric doses of clonidine are calculated based on the child’s body weight. Clonidine dosage for ADHD in children is 5 micrograms per kilogram of body weight per day orally in four divided doses. Children who require a daily dosage of 0.2 mg usually can use the 0.3 mg dermal patch. If ADHD is associated with sleep disturbances, low to moderate doses of clonidine can be taken at bedtime. Oral doses in children with Tourette’s syndrome range from 3 to 6 micrograms per kilogram of body weight per day divided into two to four even doses.

Precautions

Clonidine should not be used by people who have a known allergy to this drug. If a person has underlying depression, clonidine should be used with caution and under close physician supervision.

Clonidine should not be abruptly withdrawn but rather, slowly decreased over several days to avoid withdrawal symptoms. Withdrawal symptoms include increases in blood pressure, irritability, nervousness, insomnia, and headache. Because of the possibility of withdrawal, clonidine should not be used in patients who are unwilling or unable to follow the prescribing information.

Clonidine should be used only with caution and close physician supervision in patients with chronic renal failure, coronary artery disease, and in patients with preexisting eye problems. Often people with kidney disease should take a reduced dosage. Clonidine should not be used by pregnant women, except in the rare case where the benefits of taking clonidine outweigh the risks to the developing fetus.

Side effects

The most common side effect associated with clonidine is dizziness associated with sudden changes in position such as standing up rapidly. In order to avoid this, atients should stand up slowly. People using the dermal patch may develop rash, hair loss, a burning sensation on the skin, or other skin irritations where the patch is applied. Switching to tablets may not completely eliminate these skin problems, however.

Clonidine can cause dry mouth, constipation, nausea, daytime sleepiness, weakness, and lethargy. These side effects may take several weeks to disappear. In some cases, these side effects can be eliminated with dosage readjustment. In addition, clonidine may cause eye dryness, loss of sex drive, and decreased sexual activity.

If patients experience weight gain in the beginning of therapy, they can expect this side effect to decline over a period of several days to weeks.

Interactions

Clonidine’s blood pressure-lowering effects may be enhanced by other drugs that lower blood pressure. Conversely, the blood pressure-lowering effects of clonidine may be negated by many antidepressants.

Definition

Clonazepam belongs to a group of drugs called benzodiazepines. Benzodiazepines are medications that help relieve nervousness, tension, symptoms of anxiety, and some types of seizures by slowing the central nervous system. In the United States, clonazepam is sold under brand name Klonopin.

Purpose

Although clonazepam is approved by the United States Food and Drug Administration (FDA) for the treatment of panic disorder and some types of epilepsy, it is also used to treat social phobia, mania, and post-traumatic stress disorder.

Description

Clonazepam belongs to a group of drugs called benzodiazepines. Benzodiazepines are sedative-hypnotic drugs that help to relieve nervousness, tension, anxiety symptoms, and seizures by slowing the central nervous system. To do this, they block the effects of a specific chemical involved in the transmission of nerve impulses in the brain, decreasing the excitement level of the nerve cells.

When clonazepam is used to treat panic disorder, it is more sedating than alprazolam, another benzodiazepine drug used to treat panic disorder. However, unlike alprazolam, clonazepam may trigger depressive episodes in patients with a previous history of depression. In people who experience social phobia, treatment with clonazepam reduces the rate of depression. The use of clonazepam for social phobia is considered off-label use—a use that is legal, but not specifically approved by the FDA.

Clonazepam comes in 0.5 mg-, 1 mg-, and 2 mg tablets.

Recommended dosage

For panic disorder, the initial recommended dose is 0.25 mg twice daily. This dose can be increased every three days in increments of 0.125–0.25 mg twice daily. The target dose for panic disorder is 1.0 mg per day, although some people benefit from doses up to a maximum of 4 mg per day. When a person stops taking clonazepam, the drug should be gradually discontinued by decreasing the dose by 0.125 mg twice daily every three days.

Although clonazepam is not FDA-approved for the treatment of post-traumatic stress disorder, doses in the range of 0.25–3 mg daily appears to help treat symptoms of this disorder. Daily dosages for the treatment of social phobia range from 1.0–2.5 mg, while the dosage to control mania may be as high as 10 mg daily.

Precautions

Women who are pregnant should not use clonazepam, because it may harm the developing fetus. Clonazepam should never be taken by people who have had an allergic reaction to it or another benzodiazepine drug such as diazepam (Valium). People with narrow-angle glaucoma or severe liver disease should not take clonazepam. People who have kidney disease may need to take a reduced dosage of the drug. Saliva production may increase while taking clonazepam. Because of this, people with respiratory disease or an impaired gag reflex should use clonazepam with close physician supervision.

Because clonazepam is a nervous system depressant, it should not be taken with other such depressants, such as alcohol, other sedatives, sleeping pills, or tranquilizers. People taking clonazepam may feel unusually drowsy and mentally sluggish when they first start taking the drug. They should not drive, operate dangerous machinery, or engage in hazardous activities that require mental alertness until they see how clonazepam affects them. This excessive sedation usually goes away after a short time on the drug.

People who have underlying depression should be closely monitored while taking clonazepam, especially if they are at risk for attempting suicide.

Side effects

The main side effects of clonazepam are sedation, dizziness, impaired coordination, depression, and fatigue. Some people experience decreased sex drive while taking clonazepam.

A small number of people develop sinus problems and upper respiratory tract infections while taking clonazepam. One of the side effects of clonazepam may be increased salivation. This may cause some people to start coughing while taking clonazepam. Clonazepam may also cause anorexia and dry mouth. It may cause either constipation or diarrhea. There are a few reports of clonazepam causing menstrual irregularities or blurred vision.

Interactions

Clonazepam may increase the sedative effects of other drugs that depress the central nervous system such as certain pain strong medicines (opiates such as codeine, oxycodone, hydromorphone) and antihistamines (found in many cold and allergy medications). The sedative effect is also increased if clonazepam is taken with alcohol.

Disulfiram (Antabuse), a medication used to treat alcohol dependence, increases the effect of clonazepam. Medications that make clonazepam ineffective include phenobarbital, phenytoin, carbamazepine, theophylline, rifampin, and rifabutin.

Definition

Clomipramine is an antidepressant drug used primarily to alleviate obsessions and compulsions in patients with obsessive-compulsive disorder. Clomipramine is also used in the treatment of depressive disorders and in a number of other psychiatric and medical conditions. In the United States, the drug has also been known by the brand name Anafranil.

Purpose

Clomipramine is principally used in the treatment of the obsessions and compulsions of obsessive-compulsive disorder (OCD), when these symptoms greatly disrupt the patient’s daily activities. Obsessions are repetitive thoughts and impulses, and compulsions are repetitive behaviors. Patients with OCD find these experiences inappropriate, distressing, and time-consuming.

Clomipramine may also be used in the treatment of depressive disorders, especially when associated with obsessions and compulsions, in panic disorder, pain management, sleep attacks (narcolepsy and cataplexy), and anorexia nervosa. The drug may help to reduce compulsive behaviors in a variety of disorders with such symptoms, including trichotillomania(hair-pulling), onychophagia (nail-biting), Tourette’s disorder (tics and vocalizations), and childhood autism.

Description

Clomipramine is one of the tricyclic antidepressants, so-called because of the three-ring chemical structure common to these drugs. In the 1940s and 1950s, pharmaceutical researchers synthesized a number of new compounds for possible medical use as antihistamines and sedatives. After testing in animal experiments, a few of these substances were selected for human study. One potential drug, a tricyclic compound called imipramine, was not useful in calming agitation, but it had a striking effect in improving the mood of certain patients with depression.

Since the discovery of imipramine, many other tricyclic antidepressants have been developed with somewhat differing pharmacological activities and side effect profiles. Within this group of drugs, clomipramine is exceptionally potent in affecting levels of serotonin in the brain. In this action, it is similar to serotonin-selective antidepressant drugs, like fluoxetine(Prozac), which act specifically on serotonin levels and are effective in OCD. Serotonin is a messenger chemical (neurotransmitter) involved in transmitting signals between nerve cells. Clomipramine reduces the effects on serotonin neurotransmission in depression and OCD symptoms.

Recommended dosage

For adults, clomipramine is administered in dosages up to a maximum of 250 mg per day. Starting with a dose of 25 mg, the dosage is increased during the first two weeks to 100 mg per day. If needed, it is further increased gradually over the next several weeks. The initial dose is low to avoid side effects, and it is increased slowly to permit the patient to develop tolerance or adapt to side effects that may occur.

Older patients (over age 65), children, and adolescents are more sensitive to the side effects and toxicities of tricyclic antidepressants such as clomipramine. The maximum daily dose is usually lower for elderly patients than younger adults. For children and adolescents, the maximum recommended daily dose is the lesser of 100 mg or 3 mg per kg of body weight.

Precautions

Epileptic seizures are the most important risk associated with clomipramine. Among patients taking the drug for six months or more, more than 1% may experience seizures. The risk of seizure increases with larger doses, and seizures have been reported to occur following abrupt discontinuation of the medication. Caution and physician supervision is required if the patient has a history of epilepsy or some other condition associated with seizures, such as brain damage or alcoholism.

Clomipramine and other tricyclic antidepressants often cause drowsiness. Activities requiring alertness, such as driving, should be avoided until patients understand how the drug affects them. Dizziness or light-headedness may occur on arising from a seated position, due to sudden decreases in blood pressure. Fainting may also occur. Some patients, especially men with prostate enlargement, may experience difficulty urinating. Glaucoma may be worsened. Sensitivity to ultraviolet light may increase, and sunburns may occur more easily.

Tricyclic antidepressants, including clomipramine, should be used with caution and physician supervision in patients with heart disease, because of the possibility of adverse effects on heart rhythm. Adverse effects on the heart occur frequently when tricyclics are taken in overdose. Only small quantities of these drugs should be given to patients who may be suicidal.

Tricyclic antidepressants may cause dry mouth, due to decreased saliva, possibly contributing to the development of tooth decay, gum disease, and mouth infections. Patients should avoid sweets, sugary beverages, and chewing gum containing sugar.

It has not been determined whether clomipramine is safe to take during pregnancy, and the patient’s need for this medicine should be balanced against the possibility of harm to the fetus. Tricyclic antidepressants may be secreted in breast milk and may cause sedation and depress breathing of a nursing infant.

Side effects

Clomipramine may cause many side effects. Initially, the side effects of tricyclic drugs may be more pronounced, but sensitivity often decreases with continued treatment.

The following more common side effects are grouped by the body system affected:

• Cardiovascular: decreases of blood pressure on arising, which may cause dizziness or fainting, increases of blood pressure, rapid heart rate, pounding heart, altered heart rhythm.
• Nervous system: sedation, dizziness, headache, confusion, nervousness, restlessness, sleep difficulties, numbness, tingling sensations, tremors, twitches, increased seizure tendency.
• Digestive system: dry mouth, nausea, loss of appetite, indigestion, and constipation.
• Autonomic: blurred vision, increased sweating.
• Genital/urinary: difficulty urinating, menstrual pain, ejaculatory difficulty, impotence, decreased sex drive.
• Skin: rashes, sensitivity to sunlight.
• Body as a whole: fatigue, weight gain, flushing.

Less commonly, tricyclic drugs may cause adverse effects on almost any organ or system of the body, particularly the blood, hormones, kidney, and liver. Patients should consult their physicians if symptoms develop or bodily changes appear.

Interactions

Tricyclic antidepressants, such as clomipramine, may interact with many other drugs. Patients should inform their physicians about all other drugs they are taking before starting treatment.

Clomipramine may intensify the effects of other drugs that act on serotonin levels, possibly producing serotonin syndrome, a rare but dangerous condition with fever, sweating, tremors, and changes in mental state. Drugs that may interact this way include other antidepressants, especially selective serotonin re-uptake inhibitor (SSRI) drugs and monoamine oxidase (MAO) inhibitors. These drugs should not be taken within two weeks of taking clomipramine. Other drugs to avoid include lithium, alprazolam(Xanax), fenfluramine (Pondimin), amphetamine, dextromethorphan (used in cough suppressants), meperidine (Demerol), and tramadol (Ultram).

Tricyclic drugs may intensify the effects of other drugs causing sedation, including alcohol, barbiturates, narcotic pain medications, minor tranquilizers, and antihistamines. Tricyclics may cause excessive reductions of blood pressure in patients taking blood pressure medicine, especially on arising or standing up. Conversely, these drugs may interfere with the pressure-reducing effects of certain other blood pressure medicines and may necessitate an adjustment in dosage. Tricyclics may interact with thyroid medications to produce abnormalities of heart rhythm. Concurrent use of tricyclic antidepressants with other psychiatric medicines may result in intensification of certain side effects.

Certain drugs may interfere with the elimination of tricyclic antidepressants from the body, causing higher blood levels and increased side effects. This effect may occur with cimetidine (Tagamet), other antidepressants, methylphenidate(Ritalin, Concerta), and some antipsychotic medications.

Definition

The Clinical Assessment Scales for the Elderly, often abbreviated as CASE, is a diagnostic tool used to deter mine the presence of mental disorders and other conditions in elderly adults.

Purpose

The CASE is used to determine the presence of mental disorders in an elderly person as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (2000), which is also called DSM-IV-TR. The DSM-IV-TR is the basic reference work consulted by mental health professionals when making a diagnosis. The CASE, which is used with adults between the ages of 55 and 90, consists of a self-report form in which the person answers questions about himself or herself related to various scales. If the elderly adult is unable to complete the form because of cognitive or physical deficiencies, an other-rating form is provided for use by a knowledgeable caregiver, such as a spouse, child, or health care worker.

The CASE is not always used specifically for diagnosing mental disorders. It may be administered simply as a general assessment tool to gain insight about an elderly person. It may serve as a neurological screening tool to rule out other problems. The test makers also claim that it can be used as an early screening tool for dementia and thus allow elderly adults to receive medications to slow the progress of Alzheimer’s disease.

Description

The Clinical Assessment Scales for the Elderly were written by Cecil Reynolds and Erin Bigler. The most recent version of the test was published in 2001. The CASE consists of 10 clinical scales that measure the following: Anxiety; Cognitive Competence; Depression; Fear of Aging; Obsessive-Compulsiveness; Paranoia; Psychoticism; Somatization; Mania; and Substance Abuse. The degree to which an elderly person exhibits symptoms in these areas can help a mental health professional with the process of differential diagnosis for a mental disorder.

The CASE also includes three validity scales. These are helpful in evaluating the consistency of a person’s responses and whether the person is faking his or her answers.

The person who is completing the CASE, whether they are using the self-rating or the other-rating form, responds to the test’s written items. The test usually takes between 20–40 minutes to finish, but it is not timed. People are generally given as much time as they need to complete it.

A shorter version of the test, called the Clinical Assessment Scales for the Elderly-Short Form (CASESF) is also available. The CASE-SF takes about 20 minutes to complete and includes all 10 of the clinical scales.

Results

Scoring for the CASE is relatively simple. Scores are calculated for each scale and then compared to age-appropriate scores to determine the presence or severity of symptoms. For example, if a person scores high on the Depression scale, this information could be used as part of an overall diagnosis for a DSM-IV depressive disorder. A person scoring high in Psychoticism may have a psychotic disorder. For any specific DSM-IV diagnosis to be made, however, all of the required criteria for that disorder must be met. The results from the CASE may satisfy only some of the requirements.

The Fear of Aging scale assesses the person’s degree of apprehension or concern about the aging process. It is not necessarily related to a particular DSM-IV disorder. Information about a person’s fear of aging, however, may be helpful during the diagnostic process. It may also be useful information for a psychotherapist or other counselor, to understand the patient’s concerns or to measure progress in therapy.

The CASE was standardized using a sample of 2000 adults in the United States, 1000 for each of the two test forms. The test has been shown to have good reliability and validity. For example, scores from the CASE Depression scale have been shown to correlate very well with scores on the widely used Beck Depression Inventory, or BDI.

Definition

Circadian rhythm sleep disorder is a persistent or recurring pattern of sleep disruption resulting either from an altered sleep-wake schedule or an inequality between a person’s natural sleep-wake cycle and the sleep-related demands placed on him or her. The term circadian rhythm refers to a person’s internal sleep and wake-related rhythms that occur throughout a 24-hour period. The sleep disruption leads to insomnia or excessive sleepiness during the day, resulting in impaired functioning.

The Fourth Edition Text Revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IVTR, a handbook used by mental health professionals to diagnose mental disorders) defines circadian rhythm sleep disorder as one of several primary sleep disorders. Within the category of primary sleep disorders, it is classified as one of the dyssomnias, characterized by irregularities in an individual’s quality, timing, and amount of sleep. In earlier versions of the DSM, the disorder is called sleep-wake schedule disorder.

Description

Circadian rhythm sleep disorder involves an alteration of an individual’s circadian system or a mismatch between a person’s natural, or endogenous, circadian system and the external, or exogenous, demands placed on it. It can lead to insomnia at certain times of the day or excessive sleepiness throughout the day. The insomnia or excessive sleepiness results in impaired functioning in social, occupational, or other environments.

The DSM-IV-TR lists four types of circadian rhythm sleep disorder: delayed sleep phase type, jet lag type, shift work type, and unspecified type.

Causes and symptoms

Causes

The delayed sleep phase type of circadian rhythm sleep disorder is marked by a delay of the sleep-wake cycle as it relates to the demands of society. It is often due to a psychosocial stressor (an event in a person’s environment that causes stress or discomfort), especially for adolescents. The delayed sleep-wake cycle leads to chronic sleep deprivation and habitually late sleeping hours. Individuals with this type often have difficulty changing their sleeping patterns to an earlier and more socially acceptable time. Their actual sleep, once it begins, is normal. It is the timing of their sleeping and waking that is persistently delayed.

The jet lag type of circadian rhythm sleep disorder is characterized by disruptions arising from a mismatch between a person’s circadian cycle and the cycle required by a different time zone. The more time zones that are traveled, the greater the disruption. Eastbound travel, in which sleep-wake hours are advanced, typically causes more problems than westbound travel, in which sleep-wake hours are delayed. People who travel often and cross many time zones when they travel are most susceptible to this type.

The shift work type of circadian rhythm sleep disorder is distinguished by disruptions due to a conflict between a person’s endogenous circadian cycle and the cycle required by shift work. Individuals who work the night shift often experience this problem, especially those people who switch to a normal sleep schedule on days off. Also, people who work rotating shifts experience this problem because of the changing sleep-wake schedules they experience. The disruptions caused by shift work result in inconsistent circadian schedules and an inability to adjust to the changes consistently.

 

The unspecified type of circadian rhythm sleep disorder is characterized by a pattern of sleep-wake disturbance and circadian mismatch that is not due to the causes of the other three types. Examples of other causes include irregular sleep-wake patterns and non-24-hour sleep-wake patterns. If an individual’s sleep-wake pattern is based on a period of time of slightly more than 24 hours, their circadian rhythm can become progressively delayed.

Definition

Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant drug that is sold in the United States under brand name Celexa.

Purpose

Citalopram is approved by the United States Food and Drug Administration (FDA) for the treatment of depression. It appears to be very effective in the treatment of panic disorder and is being evaluated for the treatment of obsessive-compulsive disorder, alcohol abuse, headache, post-traumatic stress disorder, and premenstrual syndrome.

Description

Serotonin is a brain chemical that carries nerve impulses from one nerve cell to another. Researchers think that depression and certain other mental disorders may be caused, in part, because there is not enough serotonin being released and transmitted in the brain. Like the other SSRI antidepressants, fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil), citalopram increases the level of brain serotonin (also known as 5-HT). Increased serotonin levels in the brain may be beneficial in patients with obsessive-compulsive dirder, alcoholism, certain types of headaches, post-traumatic stress disorder (PTSD), premenstrual tension and mood swings, and panic disorder.

Citalopram is available in 20-mg, 40-mg, and 60-mg tablets.

Recommended dosage

The daily dosage of citalopram for depression ranges from 20–60 mg. The initial dosage is usually 20 mg per day. This dosage may then be increased to 40 mg per day at an interval of no less than one week. Most patients experience relief from depression at this dosage and do not require more than 40 mg per day. The dosage is taken once daily, either in the morning or in the evening.

Patients who are being treated for panic disorder receive doses ranging from 20–60 mg daily. A dosage of 20–30 mg daily appears to be optimal for the treatment of most panic disorders.

Precautions

Patients who are allergic to citalopram, any other SSRI drug, or any component of the preparation should not take citalopram.

Patients with liver problems and elderly patients (over age 65) need to take smaller amounts of the drug. Dosage for these patients should start at 20 mg but can be increased to 40 mg daily if needed. Patients with kidney problems do not need dosage adjustments. Patients with history of mania, suicide attempts, or seizure disorders should start citalopram with caution and only under close physician supervision. There is no clinical data available on the use of citalopram in children and adolescents.

Side effects

More than 15% of patients develop insomnia while taking citalopram. Nausea and dry mouth occur in about 20% patients being treated with citalopram. Patients also experience tremor, anxiety, agitation, yawning, headaches, dizziness, restlessness, and sedation with citalopram therapy. These side effects usually diminish or disappear with continued use of the drug, although it may take up to four weeks for this to occur.

A drop in blood pressure and increased heart rate have been associated with citalopram use. In general, patients do not experience weight gain or loss after starting citalopram.

Sexual dysfunction, which includes decreased sex drive in women and difficulty ejaculating in men, is also associated with the use of citalopram. In some patients, it may take up to 12 weeks for these side effects to disappear. In some patients these sexual side effects never resolve. If sexual side effects continue, the dose of citalopram may be reduced, patients can also have drug holidays where the weekend dose is either decreased or skipped, or they can discuss with their physician the risks and benefits of switching to another antidepressant.

Interactions

Citlopram interacts with a long list of other medications. Anyone starting this drug should review the other medications they are taking with their physician and pharmacist for possible interactions. Patients should always inform all their health care providers, including dentists, that they are taking citalopram.

Certain antifungal medications such as itraconazole, fluconazole, ketoconazole, as well as the antibiotic erythromycin, can increase the levels of citalopram in the body. This can cause increased side effects. Levomethadyl, a medication used to treat opioid dependence, may cause toxicity to the heart if used together with citalopram.

Serious side effects called serotonin syndrome have resulted from the combination of antidepressants such as citalopram and members of another class of antidepressants known as monoamine oxidase (MAO) inhibitors. Serotonin syndrome usually consists of at least three of the following symptoms: diarrhea, fever, sweatiness, mood or behavior changes, overactive reflexes, fast heart rate, restlessness, shivering or shaking. Because of this, citalopram should never be taken in combination with MAO inhibitors. MAO inhibitors include isocarboxazid, nialamide, pargyline, selegiline, phenelzine, procarbazine, iproniazid, and clorgyline. Patient taking any MAO inhibitors, should stop the MAO inhibitor then wait at least 14 days before starting citalopram or any other antidepressant. The same holds true when discontinuing citalopram and starting an MAO inhibitor.

Buspirone, an anti-anxiety medication, should not be used together with citalopram. Ginkgo biloba and St. John’s Wort, herbal supplements that are common in the United States, should not be taken together with citalopram.

Definition

Chlorpromazine is an antipsychotic drug. It is a member of the phenothiazine family of compounds and is used to alleviate the symptoms and signs of psychosis. Psychosis is a form of severe mental illness, which is characterized by loss of contact with reality, hallucinations, delusions, agitation, and unusual behavior. In the United States, chlorpromazine is also sold under the brand name Thorazine.

Purpose

Chlorpromazine is principally used to reduce the signs and symptoms of psychosis. For this purpose, the drug is used in schizophrenia and the manic phase of bipolar (formerly manic-depressive) disorder. The drug is also used in the management of severe behavioral disorders with aggression, combativeness, or excessive excitability. Chlorpromazine may sometimes be used as a sedative in non-psychotic patients with excessive anxiety and agitation. In addition, the drug has been used to relieve nausea, vomiting, and persistent hiccups.

Description

Chlorpromazine was the first antipsychotic drug. It is not an exaggeration to say that the development of this medication began a revolution in the treatment of severe mental illness, which continues to this day. Patients with schizophrenia and other psychoses, who once would have been considered hopelessly untreatable and relegated to the back wards of state institutions, are often able today, as a result of treatment with chlorpromazine or similar medications, to live in the community and lead fuller lives.

The discovery of chlorpromazine resulted from efforts of pharmaceutical researchers in the first half of the twentieth century to develop sedative medications. Several drugs of a chemical class known as phenothiazines were investigated and shown to be effective sedatives, but they had little effect on agitated patients with psychosis. A new phenothiazine drug, chlorpromazine, was synthesized in France in 1950 and was tested on such patients. In 1952, two French psychiatrists, Delay and Deniker, announced that the drug exerted a specific effect in diminishing the symptoms and signs of psychosis in patients with severe mental illnesses.

The mechanism of action of chlorpromazine is not completely understood. Its antipsychotic effects are believed to be related to its action in selectively blocking the transmission of nerve impulses from cell to cell in a region of the brain called the limbic system. This part of the brain is involved with emotions and motivation.

Chlorpromazine, when sold under the name Thorazine, is available in many forms: tablets of 10, 25, 50, 100, and 200 mg; spansules (sustained release capsules) of 30, 75, and 150 mg; ampules for injection of 25 and 50 mg; multidose vial of 10 mL of 25 mg/mL; syrup 10mg/5mL, 4 fl oz.; suppositories of 25 and 100 mg. Generic chlorpromazine manufacturers may supply a somewhat different set of dosages and products.

Recommended dosage

For acutely disturbed adult patients suffering from a psychosis, such as schizophrenia or mania, the usual daily dosage ranges from 100 mg to 1000 mg per day. Some patients may require a higher dosage. There is great variation in individual dosage requirements for chlorpromazine and for other antipsychotic medications. It is usually advisable to begin with a lower dosage, and increase the dosage until sufficient reduction of symptoms is achieved. Maximum reduction of symptoms may take many weeks of continued treatment. Because of the possibility of side effects, which may be severe, lower dosages should be used in outpatients, children, the elderly, and patients with serious health problems. For non-psychotic patients with excessive anxiety or agitation, amounts used are generally less than 200 mg per day, divided among two or three doses.

For nausea and vomiting in adults, the usual dosage is 10–25 mg every four to six hours as needed, given by injection. Alternatively, doses of 50–100 mg may be given rectally. Persistent hiccups may be treated with 25–50 mg three or four times per day, orally or by injection.

Precautions

Elderly patients (those over age 65), especially women, and patients receiving long-term antipsychotic treatment are prone to develop tardive dyskinesia. This syndrome consists of involuntary, uncoordinated movements that may not disappear or may only partially improve after the drug is stopped. Tardive dyskinesia involves involuntary movements of the tongue, jaw, mouth or face or other groups of skeletal muscles. Tardive dyskinesia may also appear after chlorpromazine use has stopped. There is no known effective treatment for tardive dyskinesia, although gradual (but rarely complete) improvement may occur over a long period. The need for long-term antipsychotic medication should be weighed against the risk of tardive dyskinesia, which increases with duration of treatment.

Neuroleptic malignant syndrome (NMS), a dangerous condition with high fever, muscular rigidity, rapid pulse, sweating, and altered mental state, may occur with antipsychotic medication. NMS requires immediate medical treatment.

Phenothiazine drugs, such as chlorpromazine, may cause sedation and may interfere with driving and other tasks requiring alertness. They may increase the effects of alcohol and sedatives. The adverse effects of chlorpromazine may be increased in people with diseases of the heart, liver, or kidney, or other debilitating illnesses. Phenothiazines may lower the seizure threshold, making it more likely that a seizure will occur in people who have a history of seizures. People with epilepsy may require adjustment of their anti-seizure medications. Chlorpromazine may cause acute muscle spasms, particularly of the head and neck, and sudden decreases of blood pressure. Patients may need to be hospitalized during the initial phase of treatment, particularly when receiving high doses or treatment by injection.

Chlorpromazine reduces the body’s ability to sweat, thus interfering with the regulation of body temperature. This may be a problem for some people in very hot weather. The problem most commonly occurs in elderly people in hot buildings without air conditioning. Body temperature may reach fatal levels. People taking chlorpromazine should be aware of the possibility of developing hyperthermia (high body temperature) in very hot weather. They should seek cool places in very hot weather.

Children may especially susceptible to neurologic reactions to phenothiazines, such as muscle spasms. Elderly patients may be particularly sensitive to sedation, low blood pressure, and other side effects. These patients should start with lower doses and increase their dosage gradually under physician supervision. Chlorpromazine may decrease salivation in older patients, predisposing to tooth decay, gum disease and mouth infections. Candy and other sugary foods should be limited, and oral hygiene should be maintained.

Chlorpromazine, like all phenothiazines, should not be taken by pregnant women because they harm the developing fetus. Breast-feeding is not recommended while taking the drug. Phenothiazines are secreted in breast milk and may cause harm to nursing infants.

Side effects

Chlorpromazine and other phenothiazines may cause many side effects. The following more common side effects are grouped by the body system affected:

• Cardiovascular: decreases of blood pressure, especially on arising, which may cause dizziness or fainting; rapid heart rate, changes in heart rhythm and electrocardiogram.
• Nervous system: sedation, muscle spasms of the head and neck, muscle rigidity, restlessness, tremors, slowed movement, shuffling gait, increased seizure tendency.
• Digestive system: dry mouth, nausea, constipation, abnormal liver tests.
• Autonomic: blurred vision, nasal congestion, reduced sweating, difficulty urinating, problems with ejaculation, impotence.
• Hormonal: lactation, breast enlargement.
• Skin: rashes, sensitivity to sunlight.
• Body as a whole: weight gain.

Interactions

Chlorpromazine interacts with a long list of other medications. Anyone starting this drug should review the other medications they are taking with their physician and pharmacist for possible interactions. Chlorpromazine and other phenothiazines may intensify the effects of drugs causing sedation, including alcohol, barbiturates, narcotic pain medications, minor tranquilizers, and antihistamines. Similarly, chlorpromazine may cause excessive reductions of blood pressure in patients taking other medicines that lower blood pressure. Chlorpromazine may also intensify side effects of drugs that also cause blurred vision, dry mouth, diminished sweating in hot weather, and constipation. Many other antipsychotics and antidepressants cause such effects.

Chlorpromazine may enhance the effects of medications that lower the seizure threshold, such as steroid drugs, the asthma medication theophylline, and many other psychiatric drugs. Patients with epilepsy may require dosage adjustments of their anti-seizure medications. The effectiveness of medications for Parkinson’s disease may be reduced by chlorpromazine and other antipsychotics. The likelihood of changes in heart rhythm may be increased when the drug is taken with other medications that have the same effect, including other antipsychotic drugs, antidepressants, certain heart medicines, and erythromycin.

Certain drugs that are eliminated by the liver may interfere with the elimination of chlorpromazine from the body, causing higher blood levels and increased side effects. Chlorpromazine may retard the elimination of other medicines, including many antidepressants, antipsychotic drugs, and heart medications, resulting in higher levels of these other medications and possibly increased side effects.

Definition

Chlordiazepoxide is used for the treatment of anxiety. It is a member of the benzodiazepine family of compounds, which slow the central nervous system in order to ease tension or nervousness. In the United States, it is sold under the trade name of Librium.

Purpose

Chlordiazepoxide is used for the short-term relief of symptoms of anxiety and management of anxiety disorders. It is also used for treating symptoms of withdrawal from acute alcoholism and alcoholic intoxication.

Description

Chlordiazepoxide is useful when treating anxiety for short periods of time. It has sedative properties that are useful for brief periods of use. It is occasionally used to stimulate appetites and is a weak analgesic. The precise mechanism of action is not known. Several hours are needed for peak levels of the drug to be achieved. Chlordiazepoxide is available in 5-, 10-, and 25-mg capsules.

Recommended dosage

Recommended dosage varies with diagnosis. The lowest possible dosage that provides relief from symptoms should be used as the drug has a high potential to cause physiological and psychological dependence. When used in adults for the treatment of moderate anxiety, the usual oral dosage is 5–10 mg three or four times per day. When used for the treatment of more severe anxiety and anxiety disorders, the usual oral dosage is 20–25 mg three or four times per day. When used by older persons, or to relieve symptoms of preoperative apprehension or anxiety, the usual oral dosage is 5 mg two to four times per day. If used as a preoperative medication, the usual dosage is 50–100 mg via intramuscular (IM) injection. When used to treat symptoms of acute alcoholism, the usual initial oral dosage is 50–100 mg, repeated as needed until agitation is adequately controlled. The recommended maximum dosage is 300 mg per day. The usual dosage for children is 5 mg two to four times per day.

Precautions

Persons with suicidal tendencies should be closely monitored, as chlordiazepoxide may lower the threshold for action and attempting suicide. The drug has a high potential to cause physiological or psychological dependence.

Side effects

Other than physiological and psychological dependence, few adverse effects have been reported. The most commonly reported include drowsiness, confusion, and difficulty in moving. These are most common among older persons. Occasionally, transient loss of consciousness has been reported.

Other adverse effects include edema (abnormal accumulation of fluid in bodily tissues), minor menstrual irregularities, nausea, constipation and, infrequently, changes in libido (sex drive). Also, it may impair mental or physical skills needed to perform complex motor tasks. For this reason, persons using this drug are advised not to drive automobiles or operate machinery.

Interactions

Chlordiazepoxide may increase the effect of alcohol or other substances that depress central nervous system functions. For this reason, they should not be used at the same time. A small number of reports of interaction with oral anticoagulants have been received, and it may exacerbate porphyria—a group of inherited disorders in which there is abnormally increased production of substances called porphyrins.