Citalopram

Also known as

Celexa, cipramil, seropram, citadur, nitalapram

Overview

Citalopram is an SSRI sold under the brand name Celexa in the United States. Citalopram is indicated for the treatment of a major depressive disorder .

Citalopram hydrobromide belongs to a class of antidepressant agents known as selective serotonin-reuptake inhibitors (SSRIs) .

Citalopram is an antidepressive agent that is FDA approved for the treatment of depression. There is a Black Box Warning for this drug as shown here. Common adverse reactions include diaphoresis, constipation, diarrhoea, nausea, vomiting, xerostomia, dizziness, headache, insomnia, sedation, somnolence, tremor, agitation, disorder of ejaculation, fatigue .

Why take it?

Sought after effects

• relief of anxiety,
• decrease in suicidal thoughts,
• improves general quality of life,
• improvements in mood .

Undesired effects

• sexual dysfunction,
• loss of appetite,
• hypertension,
• sleep disturbances,
• withdrawal,
• dietary restrictions (for maois) .

Abuse

Celexa (citalopram) has been used in combination with moclobemide (an MAOI) to produce euphoria .

• Note - Combining MAOIs with other psychoactive drugs carries serious medical risks and can result in extremely unpleasant side-effects, overheating, nausea, confusion, heart problems, and even death .

Pharmacology

Pharmacodynamics

Citalopram is one of a class of antidepressants known as SSRIs. It is used to treat the depression associated with mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of citalopram are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Iin-vitro studies show that citalopram is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. Citalopram has no significant affinity for adrenergic (α1, α2, β), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors; antagonism of such receptors has been hypothesised to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs. The chronic administration of citalopram was found to downregulate brain norepinephrine receptors, as has been observed with other drugs effective in the treatment of major depressive disorder. Citalopram does not inhibit monoamine oxidase .

Pharmacokinetics

The single-and multiple-dose pharmacokinetics of citalopram are linear and dose-proportional in a dose range of 10 - 60 mg/day. Biotransformation of citalopram is mainly hepatic, with a mean terminal half-life of about 35 hours. With once daily dosing, steady state plasma concentrations are achieved within approximately one week. At steady state, the extent of accumulation of citalopram in plasma, based on the half-life, is expected to be 2.5 times the plasma concentrations observed after a single dose .

Absorption

Rapidly and well absorbed from the gastrointestinal tract. Peak plasma concentrations occur within 4 hours of a single orally administered dose. Food does not affect absorption .

Bioavailability

Bioavailability is 80% following oral administration .

Metabolism

Citalopram is metabolised mainly in the liver via N-demethylation to its principle metabolite, demethylcitalopram. Other metabolites include didemethylcitalopram, citalopram N-oxide, and a deaminated propionic acid derivative. However, the predominant entity in plasma is unchanged citalopram. Cytochrome P450 (CYP) 3A4 and 2C19 isozymes appear to be principally involved in producing demethylcitalopram. Demethylcitalopram appears to be further N-demethylated by CYP2D6 to didemethylcitalopram. Citalopram metabolites possess little pharmacologic activity in comparison to their parent compound and do not likely contribute to the clinical effect of the drug .

Half-life

35 hours .

Elimination

12% - 23% of an oral dose of citalopram is recovered unchanged in the urine, while 10% of the dose is recovered in the faeces .

Lethal dosage

The LD50 in rats is 2.9054 mol/kg .

Toxicity

Symptoms most often accompanying citalopram overdose, alone or in combination with other drugs and/or alcohol, included dizziness, sweating, nausea, vomiting, tremor, somnolence, and sinus tachycardia. In more rare cases, observed symptoms included amnesia, confusion, coma, convulsions, hyperventilation, cyanosis, rhabdomyolysis, and ECG changes (including QTc prolongation, nodal rhythm, ventricular arrhythmia, and very rare cases of torsade de pointes). Acute renal failure has been very rarely reported accompanying overdose. Withdrawal symptoms include flu-like symptoms, insomnia, nausea, imbalance, sensory changes and hyperactivity .

Mechanism of action

The antidepressant, antiobsessive-compulsive, and antibulimic actions of citalopram are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Citalopram blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs .

Carcinogenesis, mutagenesis, impairment of fertility

There was no evidence of carcinogenesis in mice given 20 times the recommended human dose. There was an increased risk of small intestine carcinoma in rats given 1.3 to 4 times the recommended human dose. Certain in-vitro studies found evidence of mutagenicity while others did not.

Rats fed citalopram experienced decreased mating and fertility. It is not known what implication these animal studies have for humans .

Signs of usage

• Stealing, forging or selling prescriptions,
• Taking higher doses than prescribed,
• Excessive mood swings or hostility,
• Increased or decreased need of sleep,
• Confusion and poor decision-making,
• Appearing to be high, unusually energetic or revved up, or sedated,
• Continually "losing" prescriptions, so more prescriptions must be written,
• Seeking prescriptions from more than one doctor or "doctor shopping" .

Effects

More common

• drowsiness,
• dryness of mouth,
• nausea,
• trouble in sleeping .

Less common

• abdominal pain,
• anxiety,
• change in sense of taste,
• diarrhoea,
• wind,
• headache,
• heartburn,
• increased sweating,
• increased yawning,
• loss of appetite,
• pain in muscles or joints,
• stuffy or runny nose,
• tingling, burning, or prickly feelings on skin,
• tooth grinding,
• trembling or shaking,
• unusual increase or decrease in weight,
• unusual tiredness or weakness,
• vomiting,
• excessive salivation .

Minor side-effects

Some of the side-effects that can occur with citalopram may not need medical attention. As your body adjusts to the medicine during treatment these side-effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side-effects. If any of the following side-effects continue, are bothersome or if you have any questions about them, check with your health care professional -

More common

• decrease in sexual desire or ability,
• sleepiness or unusual drowsiness .

Less common

• body aches or pain,
• change in sense of taste,
• wind,
• headache (severe and throbbing),
• heartburn,
• increased sweating,
• increased yawning,
• loss of voice,
• pain in the muscles or joints,
• sneezing,
• stuffy or runny nose,
• tingling, burning, or prickly feelings on the skin,
• tooth grinding,
• unusual increase or decrease in weight,
• watering of the mouth .

Incidence not known

• bruising,
• inability to sit still,
• large, flat, blue or purplish patches in the skin,
• need to keep moving,
• uncontrolled eye movements .

Major side-effects

You should check with your doctor immediately if any of these side-effects occur when taking citalopram -

Less common

• agitation,
• blurred vision,
• confusion,
• fever,
• increase in the frequency of urination or amount of urine produced,
• lack of emotion,
• loss of memory,
• menstrual changes,
• skin rash or itching,
• trouble breathing .

Rare

• behaviour change similar to drunkenness,
• bleeding gums,
• breast tenderness or enlargement or unusual secretion of milk (in females),
• chills,
• convulsions (seizures),
• diarrhoea,
• difficulty with concentrating,
• dizziness or fainting,
• drowsiness,
• increased hunger,
• increased thirst,
• irregular heartbeat,
• lack of energy]<
• lethargy,
• nosebleed,
• overactive reflexes,
• painful urination,
• poor coordination,
• purple or red spots on the skin,
• rapid weight gain,
• red or irritated eyes,
• redness, tenderness, itching, burning, or peeling of the skin,
• shivering,
• slow or irregular heartbeat (less than 50 beats per minute),
• sore throat,
• stupor,
• sweating,
• swelling of the face, ankles, or hands,
• talking or acting with excitement you cannot control,
• trembling, shaking, or twitching,
• trouble with holding or releasing urine,
• unusual or sudden body or facial movements or postures,
• unusual tiredness or weakness .

Incidence not known

• abdominal or stomach pain,
• back or leg pains,
• black, tarry stools,
• bloating,
• bloody stools,
• chest pain,
• constipation,
• cough,
• darkened urine,
• difficult or fast breathing,
• difficulty with swallowing,
• drooling,
• fast, slow, or irregular heartbeat,
• general body swelling,
• hive-like swelling on the face, eyelids, lips, tongue, or throat,
• hives,
• holding false beliefs that cannot be changed by fact,
• impaired consciousness, ranging from confusion to coma,
• indigestion,
• itching, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue,
• jaundice,
• loss of appetite,
• loss of bladder control,
• loss of consciousness,
• medical confusion * which is confusion as to time, place, or person,
• muscle cramps or spasms,
• muscle tightness,
• muscle twitching or jerking,
• pale skin,
• penile erections, frequent or continuing,
• recurrent fainting,
• rhythmic movement of the muscles,
• seeing, hearing, or feeling things that are not there,
• swelling of the breasts or unusual milk production,
• tenderness, pain, swelling, warmth, skin discoloration, and prominent superficial veins over the affected area,
• tightness in the chest,
• total body jerking,
• twitching, twisting, uncontrolled repetitive movements of the tongue, lips, face, arms, or legs,
• uncontrolled jerking or twisting movements,
• unusual excitement,
• vomiting of blood or material that looks like coffee grounds .

Overdose

• dizziness,
• drowsiness,
• fast heartbeat,
• nausea,
• sweating,
• trembling or shaking,
• vomiting,
• cyanosis,
• confusion,
• convulsions (seizures),
• coma,
• deep or fast breathing with dizziness,
• fainting,
• general feeling of discomfort or illness,
• loss of memory,
• muscle pain,
• slow or irregular heartbeat,
• weakness .

Risks

Black Box Warning

The FDA released a black box warning in 2007, cautioning that the usage of SSRIs may lead to increased suicidal thoughts and behaviours. The FDA warned that this problem can be especially problematic for adolescents and young adults who are on SSRIs. Doctors who prescribe SSRIs, including Celexa, must be cautious and observe patients for declining mood or thoughts of suicide, especially for young people just beginning their prescription .

Dangerous interactions

• Alcohol - Alcohol consumption should be avoided while taking Celexa. Alcohol has the potential to interfere with the effectiveness of Celexa .

Withdrawal

After abusing Citalopram for a period of time, a Citalopram psychological dependency could develop. Citalopram, like other antidepressants, is not considered to be addictive. However, if a person continues abusing Citalopram and suddenly discontinues taking the drug, something called SSRI discontinuation syndrome may be experience. SSRI discontinuation syndrome produces harsh withdrawal symptoms that happen when a person suddenly stops taking the drug, decreases the dose too rapidly, or even after skipping an individual dose . These are -

• vivid dreaming,
• nausea,
• depression,
• suicidal thoughts,
• panic attack,
• sexual dysfunction,
• cardiac arrhythmia,
• frequent urination,
• memory problems,
• tremors,
• confused thinking .

some of the consequences that may be experienced .

• anxiety,
• dizziness,
• nervousness,
• trembling or shaking .

History

Citalopram was approved in 1998 by the FDA for the treatment of major depressive disorder . Citalopram is almost exclusively found as the hydrobromide salt, which is the only form approved by the FDA .

Celexa (citalopram hydrobromide) was introduced in 1998 to treat depression .

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