Citalopram

Citalopram belongs to the class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) ¹, ², ³, ⁴. Citalopram works by increasing the amount of serotonin, a natural substance in your brain that helps maintain mental balance. Citalopram is a medication that has been used to treat depression, including major depressive disorder. Citalopram is also sometimes used to treat obsessive-compulsive disorder [OCD] (with bothersome thoughts that won’t go away and the need to perform certain actions over and over), eating disorders, alcoholism, panic disorder (condition that causes sudden attacks of extreme fear with no apparent cause), premenstrual dysphoric disorder [PMDD] (a group of physical and emotional symptoms that occur before the menstrual period each month), social anxiety disorder (extreme fear of interacting with others or performing in front of others that interferes with normal life), post traumatic stress disorder (PTSD), tingling in the hands and feet caused by diabetes nerve damage (diabetic neuropathy), and certain male sexual problems. Citalopram may be prescribed for other uses; ask your doctor for more information.

Citalopram was approved for use in the United States in 1998 and Citalopram has become one of the most widely used antidepressant medications, with more than 16 million prescriptions being written yearly ⁴, ⁵.

Citalopram is available as tablets of 10, 20 and 40 mg and in an oral solution (liquid) of 10 mg/5 mL in several generic forms and under the brand name of Celexa. Citalopram is usually taken once a day, in the morning or in the evening, with or without food. The recommended dosage of citalopram in adults is 20 mg once daily, increasing to 40 mg daily if necessary. Take citalopram at around the same time every day. Your doctor may start you on a low dose of citalopram and gradually increase your dose, not more often than once a week. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take citalopram exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Your doctor may order certain laboratory tests and electrocardiograms (ECG; a test to monitor your heart rate and rhythm) before you start taking citalopram and during your treatment with citalopram.

It may take 1 to 4 weeks before you notice the full benefit of citalopram. Continue to take citalopram even if you feel well. Do not stop taking citalopram without talking to your doctor. Your doctor will probably decrease your dose gradually. If you suddenly stop taking citalopram, you may experience withdrawal symptoms such as mood changes, irritability, agitation, dizziness, numbness, tingling or electric shock-like sensations in the hands or feet, anxiety, confusion, headache, tiredness, nausea, sweating, shaking, frenzied or abnormally excited mood, and difficulty falling asleep or staying asleep. Tell your doctor if you experience any of these symptoms while you are decreasing your dose of citalopram or soon after you stop taking citalopram.

Common side effects of Citalopram are drowsiness, dyspepsia, nausea, headache, increased sweating and sexual dysfunction. Rare, but potentially severe adverse events include suicidal ideation and behavior, prolongation of the QTc interval, serotonin syndrome, precipitation of acute mania and acute glaucoma.

How does Citalopram work?

Citalopram is a racemic dicyclic phthalane derivative designated (±)‐1‐(3‐dimethylaminopropyl)‐1‐(4‐fluorophenyl)‐1,3‐dihydroisobenzofuran‐5carbonitrile and its antidepressant effect is due to a specific inhibition of the re‐uptake of serotonin in the brain thereby increasing serotonergic activity in the central nervous system (brain and spinal cord) ⁶. Multiple studies confirm that citalopram hydrobromide is a highly selective and potent SSRI with minimal effects on the neuronal reuptake of norepinephrine (NE) and dopamine (DA) ⁷. Citalopram has no or very low affinity for a series of receptors including serotonin 5‐HT1A, 5‐HT2, dopamine D1, and D2, a1‐, a2‐, alpha- or beta-adrenergic receptors, histamine H1, muscarinic acetylcholine receptors, benzodiazepine receptors, gamma aminobutyric acid (GABA) and opioid receptors ⁸, ⁹, ¹⁰. Citalopram is a racemic mixture of both (R)- and (S)-enantiomers, whereas escitalopram consists solely of the (S)-enantiomer ¹¹.

The neurotrophic hypothesis of depression emphasizes that depression results from reduced brain-derived neurotrophic factor (BDNF), leading to neuronal loss and reduced hippocampal neurogenesis. Antidepressants elevate brain-derived neurotrophic factor (BDNF) levels, counteracting neuronal and cellular loss. Extensive research in both preclinical and clinical depression studies reveals reduced serum brain-derived neurotrophic factor (BDNF) levels in depressed individuals. Antidepressants, including citalopram, raise the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus and preferential cortex ¹².

Pharmacokinetics

Citalopram onset of action for depression is about 1 to 4 weeks. However, the complete response may take 8 to 12 weeks after treatment initiation.

Bioavailability is 80%. Citalopram tablets and oral solutions are bioequivalent. Half-life is 24 to 48 hours (average, 35 hours). However, in patients with liver impairment, mild-to-moderate kidney impairment, older age (60 or older), and those who are poor CYP2C19 metabolizers, Citalopram’s half-life notably increases. Citalopram is metabolized primarily by CYP450 3A4 and 2C19, and it exhibits weak inhibitory effects on CYP450 2D6 ¹³.

Citalopram uses

Citalopram hydrobromide is a selective serotonin reuptake inhibitor (SSRI). The primary FDA-approved clinical use for citalopram hydrobromide is for treating depression in adults. Off-label uses include alcohol use disorder, coronary arteriosclerosis, obsessive-compulsive disorder, panic disorder, postmenopausal flushing, and premenstrual dysphoric disorder. Citalopram is listed in the WHO model list of essential medicines to treat depressive disorders. According to the 2022 National Institute for Health and Care Excellence (NICE) guidelines, SSRIs should be considered the initial choice for pharmacotherapy in patients with depression ¹⁴.

FDA-Approved Indication for Citalopram

Citalopram is used for the treatment of depression in adults 18 years or older ¹⁵, ¹⁶, ¹⁷. In terms of efficacy, citalopram was more efficacious than other reference compounds like paroxetine or reboxetine, but worse than escitalopram. In terms of side effects, citalopram was more acceptable than older antidepressants, like tricyclic antidepressants ¹⁸.

Off-Label Use of Citalopram

• Obsessive-compulsive disorder (OCD) ¹⁹, ²⁰
• Panic disorder ²¹
• Generalized anxiety disorder (GAD) ²²
• Social anxiety disorder (social phobia)
• Separation anxiety disorder a mental health condition characterized by excessive fear or anxiety when separated from, or anticipating separation from, a close attachment figure, often a parent or caregiver, that is out of proportion to the situation and interferes with daily life.
• Premenstrual dysphoric disorder is a severe form of premenstrual syndrome (PMS) characterized by significant mood disturbances, irritability, and other symptoms that interfere with daily life, occurring in the week or two before menstruation ²³
• Binge eating disorder is an eating disorder characterized by frequent and recurrent binge eating episodes with associated negative psychological and social problems ²⁴
• Posttraumatic stress disorder (PTSD) ²⁵
• Premature ejaculation ²⁶
• Poststroke depression ²⁷

The advantages and disadvantages of off-label use of Citalopram depend on the patient’s condition and the clinician’s judgment.

Before taking Citalopram

You should not use Citalopram if you are allergic to citalopram or escitalopram (Lexapro), or if you also take pimozide. Do not take pimozide (Orap) while you are taking Citalopram. Using these medicines together can cause very serious heart problems.

You should know that citalopram is very similar to another SSRI, escitalopram (Lexapro). You should not take these two medications together.

Do not use citalopram if you have used an monoamine oxidase (MAO) inhibitor in the past 14 days. A dangerous drug interaction could occur. Monoamine oxidase (MAO) inhibitors include isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, rasagiline, phenelzine (Nardil), selegiline (Emsam, Zelapar), and tranylcypromine (Parnate). Wait at least 14 days after stopping an monoamine oxidase (MAO) inhibitor before you take citalopram.

Tell your doctor if you also use stimulant medicine, opioid medicine, herbal products, or medicine for depression, mental illness, Parkinson’s disease, migraine headaches, serious infections, or prevention of nausea and vomiting. An interaction with citalopram could cause a serious condition called serotonin syndrome.

To make sure citalopram is safe for you, tell your doctor if you have ever had:

• heart problems, high blood pressure, long QT syndrome (a rare heart problem that may cause irregular heartbeat, fainting, or sudden death),
• a heart attack, or if you have or have ever had a slow or irregular heartbeat, heart failure (condition in which the heart cannot pump enough blood to other parts of the body) or other heart conditions.
• a stroke
• bleeding problems
• sexual problems
• narrow-angle glaucoma. You should know that citalopram may cause angle-closure glaucoma, a condition where the fluid is suddenly blocked and unable to flow out of the eye causing a quick, severe increase in eye pressure which may lead to a loss of vision. Talk to your doctor about having an eye examination before you start taking this medication. If you have nausea, eye pain, changes in vision, such as seeing colored rings around lights, and swelling or redness in or around the eye, call your doctor or get emergency medical treatment right away.
• seizures or epilepsy
• bipolar disorder (manic depression) in you or a family member
• an electrolyte imbalance such as low levels of potassium, magnesium, or sodium in your blood.
• Liver disease: According to product labeling, the dosage needs to be reduced to 20 mg daily for patients with liver impairment.
• Kidney disease: No dose adjustment is necessary for patients with mild-to-moderate kidney impairment. Patients with severe kidney impairments should be closely monitored for possible adverse reactions.

The following nonprescription or herbal products may interact with citalopram: St. John’s wort; tryptophan; cimetidine (Tagamet); aspirin and nonsteroidal anti-inflammatory drugs (NSAIDS) such as ibuprofen (Advil, Motrin, others) and naproxen (Aleve). Be sure to let your doctor and pharmacist know that you are taking these medications before you start taking citalopram. Do not start any of these medications while taking citalopram without discussing with your doctor.

People with depression or mental illness may have thoughts about suicide. Some young people may have increased suicidal thoughts when first starting a medicine to treat depression. Stay alert to changes in your mood or symptoms. Your family or caregivers should also watch for sudden changes in your behavior.

Tell your doctor if you are pregnant, especially if you are in the last few months of your pregnancy, or if you plan to become pregnant or are breast-feeding. Taking citalopram during the last 3 months of pregnancy may harm the unborn baby, but stopping the medicine may not be safe for you. Citalopram may cause problems in newborns following delivery if it is taken during the last months of pregnancy. Do not start or stop citalopram without asking your doctor.

If you are pregnant, your name may be listed on a pregnancy registry to track the effects of citalopram on the baby.

Ask a doctor if it is safe to breastfeed while using Citalopram.

You should know that citalopram may make you drowsy and may affect your judgment, thinking, and movements. Do not drive a car or operate machinery until you know how Citalopram affects you. Alcohol can make the side effects of citalopram worse.

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to Citalopram or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children

Appropriate studies have not been performed on the relationship of age to the effects of citalopram in the pediatric population. Safety and efficacy have not been established.

Elderly

Citalopram capsules is not recommended for use in the elderly because an adjustment in the dose is not possible with the available dose strength of Citalopram.

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of citalopram in the elderly. However, elderly patients are more likely to have hyponatremia (low sodium in the blood) or syndrome of inappropriate antidiuretic hormone secretion (SIADH), which may require caution and an adjustment in the dose for patients receiving citalopram ²⁸.

Pregnancy

It is not known if citalopram can make it harder for a woman to get pregnant ²⁹. Studies in animals found that citalopram might cause some reduced fertility (ability to get pregnant) ²⁹.

Miscarriage is common and can occur in any pregnancy for many different reasons. There have been some studies that suggested taking antidepressant medications might slightly increase the chance of miscarriage. However, a study on citalopram and escitalopram did not find an increased chance of miscarriage in women taking these medications ²⁹.

Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. There are reports of more than 15,000 pregnancies exposed to citalopram or escitalopram. Overall, the available data do not suggest that citalopram or escitalopram increases the chance of birth defects. While some reports have suggested an increased chance of heart defects or other birth defects, most studies have not found an increased chance of birth defects ²⁹.

Some studies suggest that taking citalopram or escitalopram throughout the pregnancy might increase the chance of pregnancy-related problems such as preterm birth (birth before 37 weeks of pregnancy) and low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth). However, research has also shown that when depression is left untreated during pregnancy, there could be an increased chance of pregnancy complications. This makes it hard to know if it is the medication, untreated depression, or other factors that are increasing the chance for these problems.

Some, but not all, studies have suggested that when pregnant women take SSRIs such as escitalopram or citalopram during the second half of the pregnancy, their babies might have an higher chance for a serious lung condition called persistent pulmonary hypertension. Persistent pulmonary hypertension happens in 1 or 2 out of 1,000 births. Among the studies looking at this, the overall chance for pulmonary hypertension when an SSRI was used in pregnancy was less than 1/100 (less than 1%).

One small study followed eleven babies exposed to citalopram during pregnancy. At one year of age there was no difference in their development compared to children who were not exposed to citalopram. Most studies find no increase in attention deficit hyperactivity disorder (ADHD) in children exposed to SSRIs during pregnancy. Most studies also find that SSRIs do not appear to increase the chance of autism spectrum disorder (ASD) after considering the effects of maternal depression or other factors.

Some medications taken during pregnancy are associated with withdrawal symptoms in a newborn after delivery. If you are taking escitalopram or citalopram at the time of delivery, your baby might have irritability, jitteriness, tremors (shivering), constant crying, different sleep patterns, problems with eating and controlling body temperature, and some problems with breathing. In most cases, these symptoms are mild and go away within a couple weeks with no treatment. Some babies may need to stay in the nursery or neonatal intensive care unit (NICU) until the symptoms go away. Most babies exposed to escitalopram or citalopram in late pregnancy do not have these symptoms. It is important that your doctor know you are taking these medications so that if symptoms occur your baby can get the care that is best for them.

Breastfeeding

Several studies have shown that small amounts of citalopram are found in breast milk ²⁹. There have been a few case reports of sleepiness and weight loss, but in most studies no harmful effects were seen in breastfed babies ²⁹. Studies also showed no difference in the intellectual development of babies exposed to citalopram during breastfeeding. A nursing infant should be monitored for being very sleepy (hard to wake for feeds), poor feeding and poor weight gain, especially in younger, exclusively breastfed infants and when a combination of medications for mental health are used. Be sure to talk to your doctor about all your breastfeeding questions. An alternative to Citalopram should be prescribed or you should stop breastfeeding while using citalopram.

Drug Interactions

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking Citalopram, it is especially important that your doctor know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using Citalopram with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Bepridil
• Bromopride
• Cisapride
• Dronedarone
• Fluconazole
• Isocarboxazid
• Levoketoconazole
• Linezolid
• Mesoridazine
• Methylene Blue
• Metoclopramide
• Ozanimod
• Phenelzine
• Pimozide
• Piperaquine
• Posaconazole
• Procarbazine
• Rasagiline
• Safinamide
• Selegiline
• Sparfloxacin
• Terfenadine
• Thioridazine
• Tranylcypromine
• Ziprasidone

Using Citalopram with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Aceclofenac
• Acemetacin
• Acenocoumarol
• Adagrasib
• Alfentanil
• Alfuzosin
• Almotriptan
• Amineptine
• Amiodarone
• Amisulpride
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Amphetamine
• Amtolmetin Guacil
• Anagrelide
• Anileridine
• Apixaban
• Apomorphine
• Ardeparin
• Argatroban
• Aripiprazole
• Aripiprazole Lauroxil
• Armodafinil
• Arsenic Trioxide
• Artemether
• Asenapine
• Aspirin
• Astemizole
• Atazanavir
• Azathioprine
• Azithromycin
• Bedaquiline
• Bemiparin
• Benzhydrocodone
• Benzphetamine
• Betrixaban
• Bivalirudin
• Bromfenac
• Plus many more not on this list.

Using Citalopram with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Ginkgo
• Irinotecan
• Mavacamten
• Rifampin.

Citalopram Contraindications

Citalopram is contraindicated with the concomitant use of monoamine oxidase inhibitors (MAOIs). Evidence suggests that concurrent use of citalopram alongside an monoamine oxidase (MAO) inhibitor can result in serotonin syndrome (serotonergic toxicity). Symptoms of serotonin syndrome include rigidity, hyperthermia, autonomic instability, mental status changes, and coma. Similar adverse reactions are possible in patients who abruptly switched from an SSRI to an MAOI; therefore, the recommendation is to wait 14 days after discontinuing citalopram to initiate an monoamine oxidase (MAO) inhibitor ³⁰.

Citalopram is also contraindicated in patients with hypersensitivity to the drug or excipient ³¹. Secondary to Citalopram inhibitory effects on CYP 2D6, it could hypothetically increase thioridazine concentrations, inducing dangerous arrhythmias ³². Canadian labeling for citalopram includes additional contraindications, specifically mentioning known QT interval prolongation or congenital long QT syndrome, which are not listed in the United States labeling ³³. Citalopram should not be administered in patients using urokinase, pimozide, methylene blue, linezolid, or dapoxetine. Linezolid is a reversible, nonselective monoamine oxidase inhibitor that can lead to serotonin syndrome if administered with serotonergic drugs ³⁴, ³⁵.

Citalopram Dosage

The dose of Citalopram will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of Citalopram. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage forms (capsules)

• For depression
  • Adults: 30 milligrams (mg) once a day. Your doctor may adjust your dose as needed. Do not start treatment with citalopram capsules because the only available dose strength is 30 mg. Use another dosage form of citalopram (eg, solution or tablets) for starting treatment and adjusting doses other than 30 mg once a day.
  • Older adults: Use is not recommended.
  • Children: Use and dose must be determined by your doctor.

For oral dosage forms (solution or tablets)

• For depression
  • Adults: At first, 20 milligrams (mg) once a day, taken either in the morning or evening. Your doctor may adjust your dose as needed. However, the dose is usually not more than 40 mg per day.
  • Older adults: 20 mg once a day, taken either in the morning or evening.
  • Children: Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of Citalopram, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Monitoring Before Treatment

Electrolytes, especially potassium and sodium, should be monitored and evaluated. Reevaluating electrolytes in patients at risk for electrolyte disturbances during the treatment is recommended.
QT-prolongation should be monitored. ECG is necessary for patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent acute myocardial infarction, uncompensated heart failure, or concomitant use of other QT-prolonging drugs ³⁶.

Monitoring During Treatment

• Patients need to be assessed and monitored for worsening depression, suicidality, or unusual changes in behavior during the initial few months of therapy or when the dose increases or decreases. Weekly face-to-face contact with patients during the initial first month of treatment, followed by visits every other week for the next month and ultimately at 3-month intervals, is recommended.
• Weight and growth should be monitored regularly by a clinician during treatment in children and adolescents.
• According to the Beers Criteria, monitor sodium levels closely when starting or adjusting the dose of citalopram in patients aged 65 and older ²⁸, ²⁸

Psychiatric Assessment for Depression and Anxiety

• Various scales in clinical practice can assist in screening anxiety disorder and depression and response to citalopram therapy.
• Patient Health Questionnaire (PHQ-9) ³⁷
• Montgomery-Asberg Depression Rating Scale(MADRS) ³⁸
• Hamilton Rating Scale for Depression(HDRS-17) ³⁹
• Generalized Anxiety Disorder 7 score (GAD-7) ⁴⁰
• Hamilton Anxiety Scale (HAM-A) ⁴¹

Citalopram side effects

Citalopram may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• nausea
• diarrhea
• constipation
• vomiting
• stomach pain
• heartburn
• decreased appetite
• weight loss
• increased sweating
• increased thirst
• frequent urination
• difficulty falling asleep or staying asleep
• drowsiness
• excessive tiredness
• yawning
• weakness
• uncontrollable shaking of a part of the body
• muscle or joint pain
• dry mouth
• sexual problems in males; decreased sex drive, inability to get or keep an erection, or delayed or absent ejaculation
• sexual problems in females; decreased sex drive, or delayed orgasm or inability to have an orgasm
• heavy menstrual periods
• runny nose

Some side effects can be serious. If you experience any of the following symptoms, or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS sections, see your doctor immediately or get emergency medical treatment:

• chest pain
• shortness of breath
• dizziness
• fainting
• fever, sweating, confusion, fast or irregular heartbeat, severe muscle stiffness or twitching, agitation, hallucinations, loss of coordination, nausea, vomiting, or diarrhea
• coma (loss of consciousness)
• hives or blisters
• rash
• itching
• difficulty breathing or swallowing
• swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
• hoarseness
• unusual bleeding or bruising
• nose bleeding
• headache
• unsteadiness
• problems with thinking, concentration, or memory
• seizures

Citalopram may decrease appetite and cause weight loss in children. Your child’s doctor will watch his or her growth carefully. Talk to your child’s doctor if you have concerns about your child’s growth or weight while he or she is taking this medication. Talk to your child’s doctor about the risks of giving citalopram to your child.

Citalopram may cause other side effects. Call your doctor if you have any unusual problems while taking citalopram.

Citalopram Toxicity

Studies reveal that citalopram toxicity is not common, even at doses up to 100 mg. However, there is a chance of developing serotonin syndrome at therapeutic doses, primarily if using another serotonergic medication concomitantly.

In the event of an intentional Citalopram overdose, the ingestion of more than 600 mg of citalopram requires 8 hours of cardiac monitoring. At the end of the observation period, the patient can be discharged if the patient is asymptomatic and QTc is less than 450 milliseconds. However, continued inpatient cardiac monitoring is necessary for patients with QTc greater than 450 milliseconds at the end of the observation period ⁴². Case reports also describe recurrent seizures associated with massive citalopram overdose. Seizures should be treated with benzodiazepines ⁴³.

Management of serotonin syndrome requires withdrawal of the citalopram and aggressive supportive treatment for hyperthermia and autonomic dysfunction. Cyproheptadine, a serotonin antagonist (5HT2 receptors), can be administered ⁴⁴.

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