Antidepressants are primarily used to manage depression and anxiety-related conditions, helping to stabilize mood, reduce symptoms like fatigue or low motivation, and support daily functioning.
They may also improve sleep, appetite, and concentration—though these benefits can vary and may come with side effects such as weight gain, sexual dysfunction, or sleep disturbances.
While most commonly prescribed for major depressive disorder, antidepressants are also used to treat conditions like generalized anxiety, panic disorder, social anxiety, PTSD, OCD, and certain medical issues such as fibromyalgia, chronic fatigue, diabetic neuropathy, and premenstrual syndrome.
This article is for informational and educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician, therapist, or other qualified health provider with any questions you may have regarding a medical or mental health condition. Never disregard professional advice or delay in seeking it because of something you have read on this site.
Antidepressants work by influencing neurotransmitters—especially serotonin, dopamine, and norepinephrine—which affect mood, motivation, and alertness.
Different medications target these chemicals in specific ways, and the choice of drug and dosage depends on the individual’s symptoms and response to treatment.
Some people may stay on antidepressants long-term, especially if symptoms return when the medication is stopped. Although these drugs are often well-tolerated, ongoing use raises important questions about long-term effects, which researchers are only beginning to explore.
Types of Antidepressants (Brief Overview)
There are several classes of antidepressants, each affecting brain chemicals slightly differently. The most common include:
- SSRIs (Selective Serotonin Reuptake Inhibitors):
Often the first-line treatment due to their relatively mild side effects. They increase serotonin availability in the brain and may cause sleep issues, weight gain, or sexual dysfunction. - SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors):
Affect both serotonin and norepinephrine levels. Side effects may include increased blood pressure, nausea, and restlessness. - TCAs (Tricyclic Antidepressants):
Older medications with stronger sedative effects. More likely to cause weight gain, dry mouth, dizziness, and sexual side effects. - MAOIs (Monoamine Oxidase Inhibitors):
Rarely prescribed today due to strict dietary restrictions and interactions. Can be effective for treatment-resistant cases.
Each class varies in side effects and tolerability. Treatment plans are tailored to the individual’s symptoms, response, and health profile.
Do antidepressants permanently alter brain chemistry?
The neuronal bases of both positive and negative effects of antidepressants, specifically SSRIs, remain poorly understood.
Researchers conducted a study of treating adult male mice with fluoxetine (a type of SSRI).
During treatment, the mice showed significant increases in day-to-day fluctuations of activity levels, often switching between hyper and hypoactivity within a few days.
As well as this, anxiety-related behaviors were observed up to 4 weeks after fluoxetine treatment stopped. When examining the brains of the mice, it was found that there was a reverse state of maturation of types of cells called granule cells in the hippocampus (an area associated with memory).
The researchers suggested that this dematuration of the hippocampus granule cells might be associated with the destabilized behaviors as a result of fluoxetine (Kobayashi, Ikeda, & Suzuki, 2011).
Other research has suggested that antidepressants can activate neuroplasticity in adult human brains.
Neuroplasticity is the ability of the brain to form and reorganize synaptic connections. This has been observed in preliminary studies showing increased neuroplasticity in the visual cortex.
Whether the effects observed in these studies are permanent is unclear. Some believe it is unlikely that antidepressants cause any permanent changes to brain chemistry in the long term.
The evidence seems to indicate that these medications cause brain changes that only persist while the medication is being taken or in the weeks following withdrawal.
Antidepressants may be used short-term for acute symptoms or long-term for chronic or recurring depression. As prescribing trends shift toward long-term maintenance, more people are taking these medications for years or even indefinitely.
Long-Term Side Effects of Antidepressants
Common Long-Term Side Effects
A study by Bet et al. (2013) found that tricyclic antidepressants (TCAs) were linked to more side effects than other classes. Reported symptoms included dry mouth and constipation. For SSRIs, the most prescribed class, common long-term effects included:
- Sexual dysfunction
- Weight gain
- Dry mouth
- Profuse sweating
In a larger study, Cartwright et al. (2016) surveyed patients who had taken antidepressants for 3–15 years. While most felt the medication helped their depression, many also reported:
- Withdrawal symptoms (73.5%)
- Sexual issues (71.8%)
- Weight gain (65.3%)
- Emotional numbness (64.5%)
- Feeling addicted (43%)
Patients expressed a need for more information about long-term risks and support when discontinuing medication.
Physical Health Risks
Long-term use—particularly of medications that affect serotonin—may increase appetite and weight, raising the risk of high blood sugar and type 2 diabetes. Higher doses of TCAs and SSRIs have been linked to worsened blood sugar control, possibly due to medication-induced weight gain.
Tolerance and Reduced Effectiveness
Some users report that antidepressants become less effective over time. While the exact cause is unclear, desensitization of brain receptors may play a role. Other contributing factors include:
- Aging
- High stress
- Substance use
- Other mental health conditions
Treatment-Resistant Depression (TRD)
In 10–30% of cases, people may not respond to standard treatment—this is known as treatment-resistant depression. TRD may stem from misdiagnosis, metabolic issues, or genetic factors, and often requires a combination of medications and therapy.
Can antidepressants cause cognitive decline?
Studies on long-term antidepressant use and cognition show mixed findings. Some observational studies report no acceleration in cognitive decline versus non-users, while one cohort found modest decline associated with SSRIs in older adults—though clinical significance was uncertain (Mo et al., 2025)
On the other hand, clinical evidence suggests some antidepressants may improve cognitive function in depressed individuals.
For example, fluoxetine has been linked to improved memory, attention, and concentration in adults, including the elderly and those recovering from brain injury (Ampuero et al., 2024).
How to manage long-term antidepressant use
Antidepressants, specifically SSRIs, which are considered the most tolerable and are, therefore, the most prescribed, are generally safe to take long-term.
The long-term effects discussed above may only occur for a small number of people, and the medication itself should disclose a list of possible side effects.
In order to manage or prevent any of the long-term negative effects from happening, there are some ways to help:
- Check-in with your doctor regularly (at least twice a year) to assess whether the antidepressants are still working as they should or if the dose needs changing.
- If wanting to stop taking the medication, only do so under the doctor’s guidance and gradually, over several months or longer. A slow withdrawal should minimize the withdrawal symptoms and make it easier to reverse the course of depression surges.
- Combine the use of antidepressants with counseling or psychotherapy such as cognitive behavioral therapy (CBT). The use of psychotherapy can teach individuals the skills they need to manage feelings of anxiety or depression and should minimize the risk of a relapse.
- Be vigilant about negative changes to identify early warning signs, such as difficulty sleeping. Noticing these changes early can allow adjustments to dosages to be made sooner.
- If presenting with TRD, depending on the case, some people may be prescribed different antidepressants, include a second type of medication where appropriate, and undertake psychotherapy or electroconvulsive therapy (ECT).
- If the medication appears to stop working, they may be advised by a doctor to either increase the dosage, change the type of medication, consider psychotherapy or make some lifestyle changes.
- If weight gain or issues with blood sugar and diabetes are prevalent, individuals may be advised to undertake physical exercise or make dietary changes to account for the weight gain experienced by some antidepressants.
Frequently Asked Questions
How long can you be on antidepressants?
The duration of antidepressant use varies depending on individual circumstances. In some cases, people may take antidepressants for several months to a year or longer, while others may require them for shorter periods.
It is important to consult with a healthcare professional to determine the appropriate duration of antidepressant treatment based on the specific needs and progress of the individual.
What happens if you take antidepressants for years?
If someone takes antidepressants for years, it is generally considered safe under medical supervision. Long-term use helps manage chronic or recurrent depression. The benefits of continued use are weighed against potential side effects and individual response.
Regular monitoring, dosage adjustments, and periodic reassessment with a healthcare professional are important to ensure the medication’s ongoing effectiveness and address any concerns that may arise.
Does your brain go back to normal after antidepressants?
After discontinuing antidepressants, the brain typically returns to its normal functioning. However, the exact timeline varies among individuals.
Withdrawal symptoms or a transient adjustment period may occur, but the brain’s neurochemical balance eventually stabilizes. It’s important to work with a healthcare professional to develop a safe and gradual tapering plan to minimize potential discontinuation effects and ensure a smooth transition.
Do you need mental health help?
USA
Contact the National Suicide Prevention Lifeline for support and assistance from a trained counselor. If you or a loved one are in immediate danger: https://suicidepreventionlifeline.org/
1-800-273-8255
UK
Contact the Samaritans for support and assistance from a trained counselor: https://www.samaritans.org/; email jo@samaritans.org .
Available 24 hours a day, 365 days a year (this number is FREE to call):
116-123
Rethink Mental Illness: rethink.org
0300 5000 927
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References
Ampuero, E., Luarte, A., Flores, F. S., Soto, A. I., Pino, C., Silva, V., Erlandsen, M., Concha, T., & Wyneken, U. (2024). The multifaceted effects of fluoxetine treatment on cognitive functions. Frontiers in Pharmacology, 15, 1412420. https://doi.org/10.3389/fphar.2024.1412420
Bet, P. M., Hugtenburg, J. G., Penninx, B. W., & Hoogendijk, W. J. (2013). Side effects of antidepressants during long-term use in a naturalistic setting. European Neuropsychopharmacology, 23(11), 1443-1451.
Cartwright, C., Gibson, K., Read, J., Cowan, O., & Dehar, T. (2016). Long-term antidepressant use: patient perspectives of benefits and adverse effects. Patient preference and adherence, 10, 1401.
Kobayashi, K., Ikeda, Y., & Suzuki, H. (2011). Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine. Molecular brain, 4(1), 1-11.
Mo, M., Abzhandadze, T., Hoang, M.T. et al. Antidepressant use and cognitive decline in patients with dementia: a national cohort study. BMC Med 23, 82 (2025). https://doi.org/10.1186/s12916-025-03851-3
