What antidepressants are available?

There are various medications for the treatment of depression. They can be split up into different groups. This article is mainly about the most commonly used antidepressants:

• Tricyclic antidepressants (TCAs)
• Selective serotonin re-uptake inhibitors (SSRIs)
• Selective serotonin noradrenaline re-uptake inhibitors (SNRIs)

Tricyclic antidepressants have been on the market the longest. They are considered to be first-generation antidepressants. SSRIs and SNRIs are second-generation antidepressants.

The following are prescribed less often:

• Adrenergic alpha-2 receptor antagonists
• Monoamine oxidase (MAO) inhibitors
• Selective noradrenaline re-uptake inhibitors
• Selective noradrenaline/dopamine re-uptake inhibitors
• Melatonin receptor agonists
• Serotonin 5-HT2C receptor antagonists

There are also the medications trazodone, tianeptine, buproprion, amgomelatine and lithium, which don't belong to any group, as well as herbal products such as St. John’s wort. A nasal spray with the active ingredient esketamine is also available that can be used in an emergency situation or if other antidepressants are not effective enough.

How do antidepressants work?

The nerve cells in our brain use various chemicals to pass on signals. Experts long believed antidepressants mostly work by improving the availability of certain chemical messengers (neurotransmitters) like serotonin and norepinephrine in the brain. It was suspected that depression results from an imbalance of those substances, which reduces some connections between the nerves. It is now unclear whether this explanation is true. Researchers now suspect that other mechanisms could play in important role in how antidepressants work.

What does the treatment involve?

Antidepressants are usually taken daily. They are started at a low dose, which is then increased. The goal in the first few weeks and months is to relieve the symptoms and, where possible, make the depression go away. Once that has been achieved, the treatment is continued for at least six to twelve months. This continuation therapy is necessary to stop the symptoms from coming back. The medication is sometimes taken for longer to prevent relapses. The duration of treatment also depends on how the symptoms continue to develop over time and whether the depression is likely to return. Some people take antidepressants over many years.

It is important to have regular appointments with your doctor when taking antidepressants. There you can talk about whether the symptoms have improved and whether there are any side effects. The doctor can check the levels of various substances in your blood by having you get regular blood tests, including how much antidepressant is in your bloodstream. The dose will be adjusted if necessary. By no means should you reduce the dose or stop taking the medication on your own. That can make the tablets less effective, or they may cause more side effects.

How is treatment with antidepressants stopped?

Towards the end of the treatment, the dose is gradually reduced over the course of about eight to twelve weeks. You may temporarily experience sleep problems, nausea or restlessness when coming off antidepressants. These symptoms often start a few days later and then go away again after two to six weeks. If that happens, doctors recommend increasing the dose back to what it was and then stopping the use of the medicine in smaller steps.

These symptoms are especially likely if you suddenly stop taking antidepressants. So their use should only be stopped quickly only if you have severe side effects.

Stopping the use of the medication as soon as you start feeling better increases the risk of the depression coming back. But unlike many sleeping pills and sedatives, antidepressants don't lead to physical dependence or addiction.

It is important to talk with your doctor regularly about how you feel while you are phasing out the medication. After you have stopped, you should check whether you still have symptoms for at least six months.

How effectively do antidepressants relieve the symptoms?

There are a lot of different medications for treating depression. But it's difficult to predict how well a particular medication will help an individual. So doctors often first suggest taking a drug that they consider to be effective and relatively well tolerated. If it doesn't help as much as expected, it's possible to switch to a different medication. Sometimes a number of different drugs have to be tried before you find one that works.

Studies show that the benefit generally depends on the severity of the depression: The more severe the depression, the greater the benefits will be. So antidepressants are an option for chronic, moderate and severe depression. They help very little or not at all in mild depression.

The various antidepressants have already been compared in many studies. Overall, the commonly used tricyclic antidepressants, SSRIs and SNRIs were found to be equally effective. Studies involving adults with moderate or severe depression have shown the following:

• Without antidepressants: About 30 out of 100 people who took a placebo noticed an improvement in their symptoms within six to eight weeks.
• With antidepressants: About 50 out of 100 people who took an antidepressant noticed an improvement in their symptoms within six to eight weeks.

Antidepressants can also relieve the long-term symptoms of chronic depressive disorder and chronic depression, and help make them go away completely.

An antidepressant can already have an effect within one or two weeks. But it may take longer for the symptoms to improve.

Depressive symptoms can also be treated with a combination of two medications. This might lead to a noticeable improvement. In some people it can take a long time for a medication to start helping. Other people still have symptoms even after trying several different medications. You can then discuss the other possible treatment options with your doctor.

How well can antidepressants prevent relapses?

Antidepressants are usually taken for one to two years, and sometimes longer, to prevent relapses. Relapse prevention may be a good idea for people who

• have already had several relapses,
• absolutely want to avoid a relapse, or
• have chronic depression.

Studies involving adults have shown that taking commonly used antidepressants such as TCAs, SSRIs or SNRIs can lower the risk of relapses, but can't completely prevent them:

• Without preventive treatment: About 50 out of 100 people who took a placebo had a relapse within one to two years.
• With preventive treatment: About 23 out of 100 people who took an antidepressant had a relapse within one to two years.

What can you do if antidepressants aren’t effective enough?

After about four weeks you can check together with your doctor whether the medicine is working and how effective it is. If it isn't, you have the following options:

• Testing your blood to see whether enough of the active ingredient is in your bloodstream
• Check whether any other illnesses or medications might be influencing its effectiveness
• Find solutions if it is difficult for you to take the antidepressant regularly
• Increase or decrease the dose
• Switch medications
• Also take another antidepressant
• Take another medication to enhance the effect of the antidepressant (e.g. antipsychotics, esketamine or lithium)
• Transcranial magnetic stimulation or electroconvulsive therapy
• Check the diagnosis and see whether you actually might have another condition
• Interrupt the treatment or stop it altogether
• Start psychotherapy, if you haven't already

You can talk with your doctor about what the best way is.

What are the side effects of antidepressants?

Like all medications, antidepressants can have side effects. Over half of all people who use antidepressants report experiencing side effects. They usually occur during the first few weeks of treatment and are less common later on.

Some of these side effects are believed to be a direct consequence of the medication's effect on the brain and are similar among various drugs within the same group. Examples include a dry mouth, headaches, dizziness, restlessness and sexual problems. These kinds of problems are often perceived to be side effects of the medications. But some of them may be caused by the depression itself.

Whether or not someone has side effects, which side effects they have, and how frequent they are will also depend on the drug and the dose used. And everyone reacts slightly differently to drugs too. The risk of side effects increases if you are also taking other medication. One of the drugs may make the side effects of the other worse. These kinds of drug interactions are common in older people and people with chronic illnesses who are taking several different kinds of medication.

For this reason, it's important to discuss the pros and cons of the various medications with your doctor.

Some side effects are more common with particular drugs:

• SSRIs are more likely than tricyclic antidepressants to cause diarrhea, headaches, sleep problems and nausea.
• Compared to SSRIs, tricyclic antidepressants are more likely to cause vision problems, constipation, dizziness, a dry mouth, trembling and difficulty urinating (peeing).

The side effects of tricyclic antidepressants are often worse than those of SSRIs and SNRIs. There's also a greater risk of severe side effects if an overdose of tricyclic antidepressants is taken.

What should you consider when deciding whether or not to take antidepressants?

Whether antidepressants are an option will depend on things like the severity of the symptoms. Other aspects can also play a role in the decision:

• Are you going to psychotherapy or are you planning to?
• Have you taken antidepressants before and did they help?
• How bad do you think the potential side effects are compared to the possible benefits?

The type of possible side effects can also be key when choosing which drug to take: Some people might be more keen to avoid digestion problems. Others might prefer to avoid dizziness, decreased sex drive or erection problems.

It only makes sense to use antidepressants if the diagnosis is correct. Specialists believe that some people are prescribed antidepressants unnecessarily. The fact that a lot more people take antidepressants nowadays suggests that this is true. They are sometimes already prescribed for milder symptoms, even though it's not clear whether they help in mild depression.

But it's still important to make sure that severe depression is diagnosed and treated properly. Antidepressants can be helpful here, and for some people may be the only way that they can get back into a daily routine or start going to psychotherapy.

Sources

• Arroll B, Elley CR, Fishman T et al. Antidepressants versus placebo for depression in primary care. Cochrane Database Syst Rev 2009; (3): CD007954. [PMC free article: PMC10576545] [PubMed: 19588448]
• Barbui C, Cipriani A, Patel V et al. Efficacy of antidepressants and benzodiazepines in minor depression: systematic review and meta-analysis. Br J Psychiatry 2011; 198(1): 11-16, suppl 11. [PMC free article: PMC3014462] [PubMed: 21200071]
• Barbui C, Esposito E, Cipriani A. Selective serotonin reuptake inhibitors and risk of suicide: a systematic review of observational studies. CMAJ 2009; 180(3): 291-297. [PMC free article: PMC2630355] [PubMed: 19188627]
• Bundesärztekammer, Kassenärztliche Bundesvereinigung (KBV), Arbeitsgemeinschaft der wissenschaftlichen medizinischen Fachgesellschaften (AWMF). Nationale Versorgungsleitlinie Unipolare Depression. AWMF-Registernr.: nvl-005. 2022.
• Davies P, Ijaz S, Williams CJ et al. Pharmacological interventions for treatment-resistant depression in adults. Cochrane Database Syst Rev 2019; (12): CD010557. [PMC free article: PMC6916711] [PubMed: 31846068]
• Fergusson D, Doucette S, Glass KC et al. Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials. BMJ 2005; 330(7488): 396. [PMC free article: PMC549110] [PubMed: 15718539]
• Fournier JC, DeRubeis RJ, Hollon SD et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA 2010; 303(1): 47-53. [PMC free article: PMC3712503] [PubMed: 20051569]
• Gartlehner G, Gaynes BN, Amick HR et al. Nonpharmacological Versus Pharmacological Treatments for Adult Patients With Major Depressive Disorder. 2015.
• Gartlehner G, Hansen RA, Morgan LC et al. Second-generation antidepressants in the pharmacologic treatment of adult depression: an update of the 2007 comparative effectiveness review. 2011.
• Geddes JR, Carney SM, Davies C et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet 2003; 361(9358): 653-661. [PubMed: 12606176]
• Hetrick SE, McKenzie JE, Cox GR et al. Newer generation antidepressants for depressive disorders in children and adolescents. Cochrane Database Syst Rev 2012; (11): CD004851. [PMC free article: PMC8786271] [PubMed: 23152227]
• Institute for Quality and Efficiency in Health Care (IQWiG, Germany). Bupropion, mirtazapine, and reboxetine in the treatment of depression: Final report; Commission A05-20C.2009.
• Institute for Quality and Efficiency in Health Care (IQWiG, Germany). Selective serotonin and norepinephrine re-uptake inhibitors (SNRI) in the treatment of depression: Final report; Commission A05-20A. 2009.
• Linde K, Kriston L, Rücker G et al. Efficacy and acceptability of pharmacological treatments for depressive disorders in primary care: systematic review and network meta-analysis. Ann Fam Med 2015; 13(1): 69-79. [PMC free article: PMC4291268] [PubMed: 25583895]
• Rayner L, Price A, Evans A et al. Antidepressants for depression in physically ill people. Cochrane Database Syst Rev 2010; (3): CD007503. [PubMed: 20238354]
• Van Leeuwen E, van Driel ML, Horowitz MA et al. Approaches for discontinuation versus continuation of long-term antidepressant use for depressive and anxiety disorders in adults. Cochrane Database Syst Rev 2021; (4): CD013495. [PMC free article: PMC8092632] [PubMed: 33886130]

• IQWiG health information is written with the aim of helping people understand the advantages and disadvantages of the main treatment options and health care services.

  Because IQWiG is a German institute, some of the information provided here is specific to the German health care system. The suitability of any of the described options in an individual case can be determined by talking to a doctor. informedhealth.org can provide support for talks with doctors and other medical professionals, but cannot replace them. We do not offer individual consultations.

  Our information is based on the results of good-quality studies. It is written by a team of health care professionals, scientists and editors, and reviewed by external experts. You can find a detailed description of how our health information is produced and updated in our methods.