The 4 Major Classes of Anxiety Medications

Medication | Anxiety and Depression Association of America, ADAA

The 4 Major Classes of Anxiety Medications

More than 1in 6 Americans take a psychiatric drug (such as an antidepressant or a sedative).

according to a 2013 Medical Expenditure Panel Survey (MEPS), which gathered information on the cost and use of health care in the United States.

Antidepressants were the most common type of psychiatric drug in the survey, with 12 percent of adults reporting that they filled prescriptions for these drugs, the study said.

Between 2011 and 2014, approximately one in nine Americans of all ages reported taking at least one antidepressant medication in the past month, according to national survey data released by the Centers for Disease Control and Prevention (CDC). Three decades ago, less than one in 50 people did. 

Variety of Medications

Four major classes of medications are used in the treatment of anxiety disorders:

Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs relieve symptoms by blocking the reabsorption, or reuptake, of serotonin by certain nerve cells in the brain. This leaves more serotonin available, which improves mood.

SSRIs (citalopram, escitalopram, fluoxetine, paroxetine, and sertraline) generally produced fewer side effects when compared with tricyclic antidepressants.  However, common side effects include insomnia or sleepiness, sexual dysfunction, and weight gain.

They are considered an effective treatment for all anxiety disorders, although the treatment of obsessive-compulsive disorder, or OCD, typically requires higher doses.

Read this blog post about SSRIs and Benzodiazepines 

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
The serotonin-norepinephrine reuptake inhibitor, or SNRI, class (venlafaxine and duloxetine) is notable for a dual mechanism of action: increasing the levels of the neurotransmitters serotonin and norepinephrine by inhibiting their reabsorption into cells in the brain.

As with other medications, side effects may occur, including stomach upset, insomnia, headache, sexual dysfunction, weight gain and minor increase in blood pressure.

These medications are considered as effective as SSRIs, so they are also considered a first-line treatment for the treatment of anxiety disorders, but not for obsessive compulsive disorder ,where SSRI’s are the preferred first line treatment.

This class of drugs is frequently used for short-term management of anxiety and as an add on treatment, in treatment resistant anxiety disorders.They are not recommended as a treatment for Post Traumatic Stress Disorder.

 Benzodiazepines (alprazolam, clonazepam, diazepam, and lorazepam) are highly effective in promoting relaxation and reducing muscular tension and other physical symptoms of anxiety.

Long-term use may require increased doses to achieve the same effect, which may lead to problems related to tolerance and dependence.

Read this blog post about SSRIs and Benzodiazepines

Tricyclic Antidepressants
Concerns about long-term use of the benzodiazepines led many doctors to favor tricyclic antidepressants (amitriptyline, imipramine, and nortriptyline).

Although effective in the treatment of some anxiety disorders(but not Social Anxiety Disorder), they can cause significant side effects, including orthostatic hypotension (drop in blood pressure on standing), constipation, urinary retention, dry mouth, and blurry vision.

Contact your physician if you experience side effects, even if you are not sure a symptom is caused by a medication. Do not stop taking a medication without consulting with the prescribing physician; abrupt discontinuation may cause other health risks.

Medications will work only if they are taken according the explicit instructions of your physician, but they may not resolve all symptoms of an anxiety disorder.

Learn more about how antidepressants work.

Ketamine (Eskatimine)

ADAA Public Statement — March 6, 2019:  On March 5, 2019 the FDA approved a new nasal spray medication- Spravato (esketamine) for treatment-resistant depression, available only at a certified doctor’s office or clinic. Ketamine represents a major step forward in the treatment of depression and suicide prevention.

ADAA recognizes that clinicians want to offer their patients evidence-based options which have passed through the numerous stages of FDA testing, and this marks the first FDA approval of a ketamine product for a psychiatric indication. This is also the first antidepressant with a novel mechanism of action that we have had in decades.


The development of the intranasal esketamine formulation with an intermittent dosing strategy offers a new approach to the treatment of refractory depression that could also impact greatly the care of patients with suicidal activity.   

While this newly approved treatment offers hope as a fast acting and durable antidepressant option for patients who have not responded adequately to conventional SSRI or SNRI medications, it is important to be cautious. Many patients may seek out esketamine have not received trials with other evidence-based treatments including pharmacotherapy and psychotherapy or rTMS or ECT. 

It is also important to note that the long-term efficacy of ketamine is not established and there is also concern about the potential abuse liability factor which will be highlighted by the FDA on the drug’s label. 

Patients considering the use of Spravato should ask their doctor what the long-term follow up strategy should be and whether there are any potential negative consequences over time with continued use. 

Additional Research Studies About Ketamine and Psychedlics: Posted April 2021

AMJ Psychiatry 2020 Issue: Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation, Roger S. McIntyre, M.D., Joshua D. Rosenblat, M.D., M.Sc., (ADAA President Elect and CMO) Charles B.

Nemeroff, M.D., Ph.D., Gerard Sanacora, M.D., Ph.D., (ADAA member) James W. Murrough, M.D., Ph.D., Michael Berk, Ph.D., M.B.B.Ch., Elisa Brietzke, M.D., Ph.D., Seetal Dodd, Ph.D.,Philip Gorwood, M.D., Ph.D., Roger Ho, M.D., M.B.B.S., Dan V. Iosifescu, M.D., Carlos Lopez Jaramillo, M.D., Ph.D., Siegfried Kasper, M.D.

, Kevin Kratiuk, B.Pharm., Jung Goo Lee, M.D., Ph.D., Yena Lee, H.B.Sc., Leanna M.W. Lui, Rodrigo B. Mansur, M.D., Ph.D., George I. Papakostas, M.D., Mehala Subramaniapillai, M.Sc., (ADAA member) Michael Thase, M.D., Eduard Vieta, M.D., Ph.D., Allan H. Young, M.Phil., M.B.Ch.B., Carlos A. Zarate, Jr., M.D.

, Stephen Stahl, M.D., Ph.D.

In this article,an international group of mood disorder experts provides a synthesis of the literature with respect to the efficacy, safety, and tolerability of ketamine and esketamine in adults with treatment-resistant depression. The authors also provide guidance for the implementation of these agents in clinical practice,with particular attention to practice parameters at point of care. Areas of consensus and future research vistas are discussed.

AMJ Psychiatry 2020 Issue: Psychedelics and Psychedelic-Assisted PsychotherapyCollin M. Reiff, M.D., Elon E. Richman, M.D., (ADAA President Elect and CMO) Charles B. Nemeroff, M.D., Ph.D., Linda L. Carpenter, M.D.

, Alik S. Widge, M.D., Ph.D., Carolyn I. Rodriguez, M.D., Ph.D., (ADAA member) Ned H. Kalin, M.D., William M. McDonald, M.D.

, and the Work Group on Biomarkers and Novel Treatments, a Division of the American Psychiatric Association Council of Research

  • Objective: The authors provide an evidenced-based summary of the literature on the clinical application of psychedelic drugs in psychiatric disorders.
  • Results: The most significant database exists for MDMA and psilocybin, which have been designated by the U.S. Food and Drug Administration (FDA) as “breakthrough therapies” for posttraumatic stress disorder (PTSD) and treatment-resistant depression, respectively. The research on LSD and ayahuascais observational, but available evidence suggests that these agents may have therapeutic effects in specific psychiatric disorders.
  • Conclusions: Randomized clinical trials support the efficacy of MDMA in the treatment of PTSD and psilocybin in the treatment of depression and cancer-related anxiety. The research to support the use of LSD and ayahuasca in the treatment of psychiatric disorders is preliminary, although promising. Overall, the database is insufficient for FDA approval of any psychedelic compound for routine clinical use in psychiatric disorders at this time, but continued research on the efficacy of psychedelics for the treatment of psychiatric disorders is warranted.

A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders, JAMA Psychiatary, April 2017, Gerard Sanacora, MD, PhD; Mark A. Frye, MD; William McDonald, MD; ADAA Board Member Sanjay J. Mathew, MD; Mason S.

Turner, MD; ADAA member Alan F. Schatzberg, MD; Paul Summergrad, MD; ADAA Board Member and Chief Medical Officer Charles B.

Nemeroff,MD, PhD; for the American Psychiatric Association (APA) Council of Research Task Force on Novel Biomarkers and Treatments

Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study, American Journal, 2018

Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD), Molecular Psychiatry, September 2018

News Articles — Ketamine

  • The Resurgence of Psychedlic Psychiatry,
  • Unmet Needs Exist in Ketamine Research,, Sanjay Mathew, MD
  • Esketamine Nasal Spray Eases Depression Symptoms In Suicidal Patients,
  • Is Ketamine an Opioid?,, Adam Kaplin, MD, PhD and Alan Schatzberg, MD
  • Esketamine Nasal Spray Effectively Treats TRD When Coupled With Antidepressants, MD Magazine
  • Ketamine isn't an Opioid and Treats Depression in a Unique Way, Science Daily, Adam Kaplin, MD, PhD
  • J&J's Ketamine-Based Drug Drives Sea Change for New Depression Treatments,, ADAA Board Member, Sanjay Mathew, MD
  • Advocates Cheer FDA Approval of Anti-Depressant Nasal Spray,, ADAA Board Member Sanjay Mathew, MD
  • FDA Approves new Johnson & Johnson Drug for Depression,, ADAA Board Member Sanjay Mathew, MD

Discussing Medications: What You Need to Know

Use these guidelines to talk to your health care professional about medications:

  • To avoid potentially dangerous drug interactions, let your mental health care provider know all medications you are taking, including prescriptions and over-the-counter drugs, herbal or dietary supplements, and vitamins. And make sure your family doctor knows you are taking medications for an anxiety disorder.
  • Learn when to take a new medication and how, such as on any empty stomach or with food, in the morning or evening, and how frequently.
  • Find out how long it should take for the medication to start working and what you should expect when this happens.
  • Ask: How will the medication help me? What side effects might occur? Should I avoid any foods or beverages? Are drug interactions with other prescriptions a possibility? How often you should see the doctor for a medication check-up?
  • Ask for the prescribing physician’s after-hours phone number in case you develop side effects.
  • A good source of information about medications and over-the-counter products is your pharmacist, who should have information about all your prescriptions to advise you about possible drug interactions, side effects, and instructions for use.

If your physician does not want to spend the time to answer your questions, you may need a referral to a different physician.

Questions to Ask About a New Drug/Treatment on the Market:

  1. Is this new drug/treatment appropriate for me?
  2. What are the drawbacks, if any of this new treatment?
  3. What might be the benefits over my current regimen?
  4. Is the price (typically high when a drug is new) worth the added benefit?
  5. Is this treatment ready for widespread use?  Meaning, does it have safety established? Do we know how long people need to be on this treatment? Do we know about any long term issues that could result from this?

ADAA Medication Information Resources

Patient-Assistance Programs for Prescription Drugs

Most pharmaceutical companies offer patient-assistance programs for uninsured patients. These programs provide prescribed medication at little to no cost. Eligibility varies; see the Partnership for Prescription Assistance website for more information, or contact companies directly about their patient assistance programs.

Reviewed/Updated July 2019


Anti-Anxiety Medications (Benzodiazepines)

The 4 Major Classes of Anxiety Medications

Anti-anxiety medications help reduce the symptoms of anxiety, such as panic attacks or extreme fear and worry. The most common anti-anxiety medications are called benzodiazepines.

Benzodiazepines are a group of medications that can help reduce anxiety and make it easier to sleep.

They are also used as a muscle relaxant, to induce sedation for surgery and other medical procedures, and in the treatment of seizures and alcohol withdrawal.

Benzodiazepines are also called minor tranquillizers, sedatives or hypnotics. They are the most widely prescribed psychoactive drugs in the world.

The calming effects of benzodiazepines can often be achieved without drugs.

Various kinds of exercise, such as walking, running, yoga or tai chi can help, as can reducing the stress in your life and taking time for relaxing activities such as meditation, reading a book or having a warm bath.

Talking with a trusted friend, family member or therapist and working out the problems that are troubling you can also help. Whenever possible, these approaches should be tried first, before benzodiazepines.

However, when non-drug approaches are not possible or do not help, benzodiazepines can provide relief.

When used appropriately, benzodiazepines are safe and effective drugs. They do, however, have potential for abuse and can be addictive. For this reason, they are usually only recommended for short-term or occasional use.

Do I need this treatment?

A certain amount of anxiety or insomnia is a normal reaction to what is happening in your life. You may worry or feel stressed, and sometimes these feelings can keep you up at night. Most often, these feelings pass and are not a problem.

However, these feelings can become a problem when they continue over a longer term, cause severe distress, make you feel physically ill and affect your behaviour. This kind of anxiety may be triggered by a challenging life event.

It can also be a symptom of a mental health problem.

The ability to fall asleep and to sleep through the night can be affected by many types of health problems. These include physical conditions that cause pain or trouble breathing, as well as mental health problems. When sleep is disrupted, health can be further affected.

While each situation is unique and different treatment approaches may be called for, benzodiazepines can help to provide relief.

What does Anti-anxiety Medications (Benzodiazepines) do?

Benzodiazepines enhance the activity of the neurotransmitter GABA—a chemical in the brain that helps you to feel calm. Their effect also produces drowsiness, making it easier to fall asleep and sleep through the night.

Side effects of Anti-anxiety Medications (Benzodiazepines)

The side-effects of benzodiazepines are generally mild and may not be noticed when these drugs are used at low doses.

Common side-effects include:

  • drowsiness
  • sedation
  • dizziness
  • loss of balance.

At higher doses, side-effects can include:

  • confusion
  • disorientation
  • amnesia
  • breathing difficulties
  • depression.

Other possible effects, which are extremely rare, include agitation, hallucinations and nightmares. Reducing the dose can help to reduce side-effects.

Benzodiazepines can make it harder to learn and remember new information and to do certain physical and mental tasks. These abilities return to normal once the effect of the drug wears off.

When used to help you get to sleep, benzodiazepines can have some “hangover” effects, such as morning and daytime drowsiness.

Types of Anti-anxiety Medications (Benzodiazepines)

Many types of benzodiazepines are available in Canada. All benzodiazepines work the same way; however, the intensity and duration of their effects vary.

Benzodiazepines most commonly used to treat anxiety disorders are clonazepam (Rivotril)*, alprazolam (Xanax) and lorazepam (Ativan). Also used are bromazepam (Lectopam), oxazepam (Serax), chlordiazepoxide (once marketed as Librium), clorazepate (Tranxene) and diazepam (Valium).

Benzodiazepines used for the treatment of insomnia include lorazepam (Ativan), nitrazepam (Mogadon), oxazepam (Serax), temazepam (Restoril), triazolam (Halcion) and flurazepam (Dalmane).

Another drug used for insomnia is zopiclone (Imovane). This drug is similar to benzodiazepines and has similar side-effects. Zopiclone may have less abuse potential than some benzodiazepines; however, people can still become addicted to this drug.

Benzodiazepines are available in the form of tablets or capsules, which are taken by mouth. Some are also available as a sublingual tablet, which is dissolved under the tongue, or as a solution for injection.

* Medications are referred to in two ways: by their generic name and by their brand or trade names. Brand names available in Canada appear here in brackets. For example, alprazolam (Xanax) and lorazepam (Ativan).

How long should I take benzodiazepines?

For most people, benzodiazepines are helpful only as a temporary measure, to be used only in the following ways:

  • on occasion, to help you sleep or when anxiety can’t be managed with non-drug approaches
  • daily, for up to a few weeks, to help re-establish sleep patterns or to reduce anxiety while waiting for an antidepressant or other treatment to take effect.

Some people may continue to use benzodiazepines for longer, even months or years.

Some do so because they continue to find these drugs helpful and have agreed with their prescribing physician that the benefits of continuing to use them outweigh the risks.

There are also those who continue to use benzodiazepines over a longer term because the prescribing doctor has not re-examined their continued use. In this instance, ask another doctor to review your prescription.

Are benzodiazepines addictive?

When used on occasion or daily for a few weeks, benzodiazepines have a low risk of addiction.

This risk increases, however, when benzodiazepines are taken regularly for more than a few weeks, especially when they are taken in higher than normal doses.

People with a history of substance abuse should avoid or minimize use of benzodiazepines as they are at higher risk of becoming addicted.

Signs of addiction include strong cravings for the effects of the drug, taking more of the drug than intended and continuing to use the drug despite the problems it may cause. Addiction may develop with or without physical dependence.

Physical dependence: When benzodiazepines are taken regularly over a long period of time, the body adapts to the presence of the drug. This is known as physical dependence. Physical dependence, on its own, is not the same as addiction. Signs of physical dependence include tolerance and withdrawal.

Tolerance: People are said to have developed tolerance to a drug when the same dose, taken over time, no longer has the desired effect. With benzodiazepines, it is known that:

  • Tolerance to the sleep-inducing effects may develop within a few weeks of regular use; however, tolerance does not usually develop with occasional use.
  • Tolerance to the anxiety-relieving effects is less ly to develop.
  • Tolerance to the effects of one type of benzodiazepine leads to tolerance to other benzodiazepines, and to other drugs with similar effects, including alcohol.

Some people who develop tolerance may take higher and higher doses to feel the same intensity of effect as when they started taking the drug. These people may find it difficult to stop using benzodiazepines.

Withdrawal: Withdrawal symptoms of benzodiazepines may be similar to the reasons why the drugs were prescribed in the first place. The severity of withdrawal symptoms depends on the type of benzodiazepine used, the amount used and length of time it is used, and on whether the drug is stopped abruptly.

Symptoms can include headache, insomnia, anxiety, tension, sweating, difficulty concentrating, tremor, sensory disturbances, fatigue, stomach upset and loss of appetite. Severe withdrawal symptoms from regular use of benzodiazepines in high doses may include agitation, paranoia, delirium and seizures.

Withdrawal symptoms generally begin within a few days after treatment is stopped, and they may continue for two to four weeks or longer.

How do I safely use benzodiazepines?

Take only as directed by your doctor; do not increase your dose.

Once you have slept well for two or three nights in a row, try to get to sleep without taking the medication.

If you have been taking benzodiazepines regularly for a few weeks or more, check with your doctor before reducing or stopping your medication.

How do I cut down or stop taking benzodiazepines?

Most often, benzodiazepines are prescribed to help people get through stressful situations or to provide relief while waiting for other treatment to take effect. When used in this way, on occasion or daily for a few weeks, most people can stop taking them without difficulty or withdrawal effects.

Stopping use can, however, be hard for some people, even when the use is short term. Problems are most ly to occur when:

  • the issues that caused you to take these drugs in the first place have not yet been dealt with
  • no other medication or talk therapy has been started.

People who wish to stop using benzodiazepines after using them regularly over a longer term will need to cut back their use gradually over an extended period of time. This approach reduces withdrawal effects and helps ensure success in stopping.

Because the ideal process for cutting down varies depending on the benzodiazepine you are taking, the dose and the length of time you have been taking it, ask your doctor to help you set up a schedule.

If the long-term use has been at high doses, stopping use requires medical supervision.

Will benzodiazepines interact with other medications?

These drugs may interact with other medications. If your doctor or dentist prescribes any medication, inform him or her about the drug you are taking. Check with your pharmacist before using any over-the-counter medication, including herbal products, cold or allergy tablets, or cough syrups.

When taken on their own, the risk of overdose with benzodiazepines is low; however, combining these drugs with other sedatives, such as alcohol, or with medications containing codeine or other opioid drugs, can result in overdose and possible death. Symptoms of overdose include slurred speech, confusion, severe drowsiness, weakness and staggering, slow heartbeat, breathing problems and unconsciousness.

What if I drink alcohol or coffee while taking benzodiazepines?

Benzodiazepines can be dangerous when combined with alcohol. Benzodiazepines increase the effects of alcohol, making you more sleepy, dizzy or lightheaded.

One danger of this is the increased risk of stumbling, falling and related injuries. Another is the increased risk of overdose.

Both alcohol and benzodiazepines slow down the central nervous system, which controls breathing. In overdose, breathing can stop.

Drinking too many caffeinated beverages (i.e., more than four cups of coffee or six cups of tea daily) may counteract the anxiety-reducing effects of benzodiazepines.

What if I use street drugs while taking benzodiazepines?

If you are taking benzodiazepines to help reduce the distress of a mental health problem, chances are that you want to feel less anxious and get a good night’s sleep. Street drugs, such as marijuana or cocaine, have effects that can worsen symptoms of anxiety and interfere with sleep—making you feel worse, rather than better.

Taking benzodiazepines to enhance the effect of other sedative drugs, such as opioids, is dangerous and increases the risk of overdose and injury.

Will benzodiazepines affect my ability to drive safely?

Benzodiazepines can affect your ability to drive a vehicle and increase the risk of a crash, especially if taken in combination with alcohol or other sedative drugs. The risk is highest when you first start taking benzodiazepines, before you are used to their effect. Avoid driving or operating other machinery if you feel drowsy or slowed down.

Will benzodiazepines affect my sex drive and function?

There is no clear evidence that benzodiazepines have any effect on sex drive or function.

Is it safe to take benzodiazepines while pregnant or breastfeeding?

The risk of birth defects from taking benzodiazepines while pregnant is not known, though it is thought to be very small. If benzodiazepines are used regularly close to the delivery date, the baby may be born drowsy or may have withdrawal symptoms such as restlessness and feeding problems.

Small quantities of benzodiazepines can be passed through breast milk from the mother to the baby. This may cause drowsiness in the baby.

If you are pregnant or breastfeeding, or thinking about becoming pregnant, talk to your doctor about the risks and benefits of continuing or stopping benzodiazepines. If your doctor recommends that you stop taking benzodiazepines, he or she will help you to slowly reduce your dose over time, to avoid withdrawal symptoms.

Can children and teens use benzodiazepines?

Benzodiazepines are not recommended for use by children and teens, except to bring sedation prior to surgery or for brief medical procedures. Extra caution should be used when considering giving benzodiazepines to children as these drugs may cause children to become irritable rather than calm.

Can older adults use benzodiazepines?

Sensitivity to the effects of benzodiazepines increases with age. When older adults take these drugs, they may become confused and have reduced muscle co-ordination, putting them at greater risk of falls, hip fractures and motor vehicle crashes.

If an older person has been taking benzodiazepines regularly for a very long time, the process required to stop taking them may be long and difficult. In some cases, a doctor may decide to leave the older person on the medication, with regular assessment of daytime side-effects.

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Types of Anxiety Medications: Uses, Side Effects, Interactions & Warnings

The 4 Major Classes of Anxiety Medications

  • Alprazolam increases blood levels of the antidepressants imipramine and desipramine. Alprazolam may also interact with some calcium channel blockers and with grapefruit juice. Carbamazepine decreases blood levels of alprazolam.
  • Combining benzodiazepines with alcohol or other central nervous system depressants can cause increased sedation and potentially dangerous respiratory depression.
  • Fluoxetine, propoxyphene, and oral contraceptives increase blood levels of alprazolam (Xanax), as do ketoconazole, itraconazole, nefazodone, fluvoxamine, and erythromycin.
  • Oral antifungal agents such as ketoconazole and itraconazole may significantly decrease blood levels of clonazepam (Klonopin).
  • Serious side effects, including respiratory arrest, may occur if lorazepam (Ativan) is combined with clozapine. Dosage of lorazepam should be halved when taken with valproate or probenecid.
  • Theophylline and aminophylline may affect the sedative effects of lorazepam.
  • Several drugs can increase the blood levels of triazolam (Halcion), including isoniazid, oral contraceptives, and ranitidine. Ketoconazole, itraconazole, and nefazodone have a profound effect on triazolam metabolism and should not be taken with it.

    Grapefruit juice also increases the amount of triazolam in the blood.

  • Triazolam may interact with calcium channel blockers, antidepressants, ergotamine, amiodarone, and cyclosporine.

Selective Serotonin Reuptake Inhibitors

  • SSRIs should not be used with MAOIs. Additionally, serotonin syndrome may occur if SSRIs are administered with triptan migraine drugs, linezolid (Zyvox), St. John's Wort, lithium, or tramadol. Combining SSRIs with aspirin, other nonsteroidal anti-inflammatory drugs, or warfarin, increases the risk of bleeding.

  • Levels of imipramine and desipramine have been shown to significantly increase when taken with certain SSRIs. Combining SSRIs with antipsychotic drugs may result in neuroleptic malignant syndrome, a serious side effect.
  • Citalopram (Celexa) may cause a significant rise in blood levels of desipramine and other tricyclic antidepressants.
  • Taking fluoxetine (Prozac) with pimozide or thioridazine is contraindicated because of possibly dangerous effects on heart rhythm. Stable levels of phenytoin and carbamazepine may rise to toxic levels if fluoxetine is introduced.
  • Plasma levels of pimozide, thioridazine, alosetron, astemizole, cisapride, diazepam, and tizanidine increased significantly when used with fluvoxamine (Luvox). Consequently, these drugs should not be used together. Additionally, dosage adjustments may be required for warfarin, mexiletine, and theophylline when used with fluvoxamine.
  • Paroxetine (Paxil) should not be used with pimozide or thioridazine because of possibly dangerous effects on heart rhythm. Digoxin, atomoxetine, risperidone, and theophylline levels may require adjustment when given with paroxetine.
  • Sertraline (Zoloft) should not be used with pimozide because of the potential for severe cardiac effects.
  • Vilazodone may cause eye pain, visual changes, and swelling in the ocular area.
  • Vilazodone and vortioxetine can affect sodium blood levels and coagulation of blood.

Tricyclic Antidepressants (TCAs)

  • TCAs should not be used with MAOIs. SSRIs may increase blood levels of TCAs, as may cimetidine. Phenytoin and barbiturates may decrease the blood levels of TCAs.

    Anticholinergic drugs may worsen some side effects of TCAs.

  • Decongestants and other drugs containing catecholamines should not be used with TCAs.

    The sedative effect of TCAs may be enhanced by alcohol and other CNS depressant drugs.


  • MAOIs interact with a wide range of prescription and nonprescription medications, including other antidepressants, anticonvulsants, antihistamines, and decongestants, as well as some foods. Many of these interactions can be fatal. Patients should inform all those involved in their care if they are using MAOIs.

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

  • SNRIs should not be used with MAOIs.
  • Heavy alcohol use with duloxetine (Cymbalta) may result in liver injury.

Other Antidepressants

  • Bupropion (Wellbutrin) should not be used with the MAOI phenelzine. Use caution when bupropion is taken with drugs known to lower the seizure threshold (for example, theophylline or steroids).

    The use of bupropion with nicotine transdermal systems may result in hypertension.

  • HIV drugs (such as ritonavir), as well as oral antifungals (for example, ketoconazole) increase plasma levels of trazodone (Desyrel). Carbamazepine reduces blood levels of trazodone.

    Blood levels of phenytoin and digoxin increased when given with trazodone.


Antihistamines may cause increased drowsiness when used with CNS depressants.

Buspirone (BuSpar)

Large amounts of grapefruit juice may increase blood levels of buspirone. Other drugs that affect blood levels of buspirone include oral antifungals, calcium channel blockers, certain antibiotics (Erythromycin and Rifampin), and nefazodone (Serzone).


Gabapentin (Neurontin) may affect blood levels of hydrocodone and morphine. Gabapentin levels can decrease when given with the antacid Maalox. Allow 2 hours between the drugs.

The following medications significantly decrease blood levels of lamotrigine (Lamictal): oral contraceptives, phenobarbital, primidone, phenytoin, carbamazepine, oxcarbazepine, and rifampin.

The following medications decrease topiramate (Topamax) levels: phenytoin, carbamazepine, valproic acid, and lamotrigine. Using topiramate with acetazolamide or dichlorphenamide may increase the risk for kidney stones. Topiramate can interact with some drugs used for diabetes (metformin, pioglitazone), so careful blood sugar monitoring is warranted when they are combined.

The following drugs may significantly increase levels of valproate (Depakote) in the blood: aspirin and felbamate. The following drugs may significantly decrease blood levels of valproate: rifampin, carbapenem antibiotics (imipenem, meropenem, ertapenem).


Beta-blockers used with other cardiac drugs — calcium channel blockers, anti-arrhythmic, ACE inhibitors, digitalis — may result in additive effects on blood pressure and heart rate, sometimes to a dangerous level.

Warfarin concentrations increase when used with propranolol.

Hypotension and cardiac arrest have occurred with the use of haloperidol and propranolol.


Sedation may increase if clonidine (Catapres) and guanfacine (Tenex) are used with other CNS depressants, including alcohol.


Increased drowsiness may occur when aripiprazole (Abilify) is given with other CNS-active drugs. Significant increases in blood levels may occur if given with oral antifungals (ketoconazole). A significant decrease in the blood level of aripiprazole may occur if given with carbamazepine.

Ziprasidone (Geodon) should not be used with other drugs known to cause prolongation of the QT interval, such as thioridazine and chlorpromazine.

The effect of blood pressure-lowering medications may be enhanced when taken with either ziprasidone or risperidone (Risperdal). These medications may decrease the effectiveness of levodopa/dopamine agonists. Increased drowsiness may occur if these drugs are combined with other CNS depressants.

Carbamazepine may decrease blood levels of ziprasidone and risperidone; ketoconazole may increase levels of ziprasidone.

The following drugs may significantly increase blood levels of quetiapine (Seroquel): oral antifungals (ketoconazole), certain antibiotics (erythromycin), and protease inhibitors (indinavir). Phenytoin and thioridazine may significantly decrease the blood levels of quetiapine.

Olanzapine (Zyprexa) should be used with caution with other CNS depressant drugs and alcohol. The following drugs may increase blood levels of olanzapine: fluvoxamine, fluoxetine, rifampin, and omeprazole.

Carbamazepine may decrease blood levels of olanzapine.

Orthostatic hypotension potential may rise if olanzapine is used with diazepam or alcohol, and olanzapine can enhance blood-pressure-lowering effects of other drugs.


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