Why does it take so long for antidepressants to work?

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In this we will try to answer the question “Why does it take so long for antidepressants to work?”

We will also discuss how long antidepressants take to work, and what can be done to improve the action of antidepressants as well as briefly discuss what antidepressants are.

Why does it take so long for antidepressants to work?

It has been long speculated that the reason why antidepressants take as long as three to six months for an individual to feel the positive psychological effects of the drug is because it is engineered to impact DNA sequence. 

Along with this hypothesis, there has been new research done that explains this particular delay in symptom alleviation is caused by “diminished levels of an important signal molecule”.

Let us take a look at both these hypotheses closely.

When it comes to the hypothesis related to genetic coding of the DNA sequence which has been the long standing explanation as to why antidepressants take so long to take effect, we consider the action of one class of antidepressants- Selective Serotonin Reuptake Inhibitors. 

The way SSRIs work is that this particular drug inhibits specific serotonin reuptake transporters by binding directly to the transporter, thus inhibiting the reuptake of serotonin. 

This increases the levels of serotonin in the brain and thus improves mood, motivation, and other positive desirable effects related to mood regulation. 

While one might think that this binding action shouldn’t take so long, which it does not, it is not just this action that is involved, rather SSRIs and other antidepressants target the genes on the DNA sequence that code for the serotonin transporter. 

The SSRI’s impact on the DNA makes these genes that influence the action of the serotonin transporter and makes them less active so that there is a decreased number of transporters in the brain and as a result, less serotonin reuptake. 

Now, our brain has a huge number of active transporters and it takes time for the antidepressants to suppress the genes that code for these transporters. 

So when we take the medication, it takes some time for the drug to take effect on the gene related to the transporters on the DNA and as a result it takes time for the levels of the serotonin to stabilise and thus impact mood and alleviate symptoms of depression. 

Another hypothesis that tries to explain the delay in the impact of antidepressants was put across by researchers at University of Illinois at Chicago led by neuroscientist Mark Rasenick.

These researchers identified an unknown mechanism of selective serotonin reuptake inhibitors, or SSRIs.

While it was believed that the first widely accepted hypothesis explained above was the action mechanism of SSRIs, these researchers in Chicago identified another aspect of SSRIs.

They observed that these inhibitors also accumulate in patches of the cell membrane called lipid rafts and it was this buildup that also leads to a decrease in the levels of a signal molecule known as “G Proteins”.

When it comes to people with depression, G proteins tend to get collected in the lipid rafts, cell membranes rich in cholesterol however,because there is a lack of cyclic AMP in these areas, these proteins do not function leading to a pampening of their signals which could be connected to apathy in depression.  

Now, when the SSRIs are adminsted, the researchers found that the SSRIs accumulate in the same places as the g-proteins- the lipid rafts which leads to the decrease in G protein levels.

The researchers hypothesised that as the SSRIs take up the space in the lipid rafts and the G proteins move out of these rafts towards other areas of the cell where they have access to Cyclic AMP which allows them to function is what causes the delay. 

How long does antidepressants take to work?

When it comes to the action of antidepressants and the improvement of symptoms, there is no conclusive timeline. The timeline differs according to context and medication used.

However, it has been observed that the initial improvements and alleviations of symptoms occur in one to two weeks starting with physical symptoms. 

So if you are taking antidepressants for depression, you might feel less lethargic, tired, and irritable. You might also start gaining an appetite or your appetite will start to stabilise as well as your sleep patterns during these first two weeks. 

However, this timeline differs according to what drug they are taking and the severity of their disorder, in fact most people might not notice any difference with the first drug and first dose they are administered. 

When it comes to the full time psychological and physical benefits of antidepressants, it might take them two to three months, sometimes six months of taking the drugs.

It is possible that psychological benefits related to mood and thoughts can start after six weeks- that is around two months, and improve over time. However, it is very likely that this happens as drug dosage is increased, or the drug itself is switched or new drugs added in combination. 

It is also possible that the positive effects or alleviation of symptoms is also accompanied by other things like psychotherapy done in conjunction with antidepressant treatment as well as lifestyle changes when the individual is motivated to change. 

What can be done to improve the effect of antidepressants? 

Here are a few things that you and your doctor can discuss and apply to your treatment with antidepressants to improve your condition:

  • Increase dosage by titrating the dosage up until you experience relief from symptoms while experiencing minimal side effects.
  • Combining medications when you do not find that increasing dosage helps. You and your doctor can discuss you taking on another form of antidepressants or atypical antidepressants.
  • Changijng medication when the first form of medication does not seem to have any effect on your condition. 
  • Lifestyle changes such as improving diet, sleep patterns and quality, and exercise. 
  • Concurrent psychotherapy since research has found that a combination treatment of therapy and antidepressants yield better results than antidepressants alone. 

What are Antidepressants?

Antidepressants are medications that were first developed in the 1950s that are used to help treat symptoms of depression, social anxiety disorder, anxiety disorders, seasonal affective disorder, and dysthymia, or mild chronic depression, as well as other conditions.

Antidepressants work to correct chemical imbalances in the brain- chemicals known as neurotransmitters that are responsible for changes in mood, behaviour, and emotions. 

By correcting and balancing the levels of these chemicals in the brain in various ways, these medicines can help improve your mood, bring positive changes related to various symptoms such as focus and concentration, sleep, appetite etc.

What are the different types of Antidepressants?

Antidepressants are of different classes or different types depending on their target and the process by which they help balance neurochemical levels in the brain. 

The different classes of antidepressants are as follows:

Selective serotonin reuptake inhibitors (SSRIs) 

These are the most commonly prescribed antidepressants because of their high levels of efficacy and low number of side effects. 

These drugs help to increase levels of serotonin in the brain by inhibiting reuptake of these chemicals by blocking the receptors. As SSRIs affect the levels of serotonin and not other neurotransmitters, they are referred to as “selective.”

The use of this class of antidepressants commonly involve a few side effects such as nausea, vomiting, diarrhea, sexual dysfunction, headache, weight gain, anxiety, dizziness, dry mouth, and trouble sleeping.

Serotonin norepinephrine reuptake inhibitors (SNRIs) 

This particular medication works by blocking the reabsorption of the neurotransmitters serotonin and norepinephrine in the brain so as to increase the levels of these neurotransmitters. 

The difference between SSRIs and SNRIs is that SNRI is not selective and may influence the levels of other neurotransmitters. 

The common side effects of SSRIs include nausea, dizziness, and sweating as well as sexual dysfunction. Other less serious side effects include tiredness, constipation, insomnia, anxiety, headache, and loss of appetite.

Tricyclic antidepressants (TCAs) 

TCAs are drugs that block the reabsorption of Serotonin and norepinephrine in the brain and they were the first approved drugs for depression; however , as of today, more efficient drugs are used that have less side effects as compared to TCAs.

Side effects of this drug include dry mouth, constipation, blurred vision, urinary retention, dizziness, tachycardia, memory impairment, and delirium, orthostatic hypotension, weight gain, seizures, bone fractures, sexual dysfunction, increased sweating, and increased or irregular heartbeats.

Monoamine oxidase inhibitors (MAOIs) 

MAOIs are drugs that work by blocking or inhibiting the activity of monoamine oxidase which is crucial in the breakdown of norepinephrine, serotonin, and dopamine in the brain and other parts of the body. 

This drug is not a primary option that many physicians prescribe because it has many drug and food interactions and also causes significant side effects. As a result, this class of drug has been replaced by newer antidepressants that are safer and cause fewer side effects.

Atypical antidepressants

This type of drugs do not fit into any of the other classes of antidepressants and each drug under this category has a unique mechanism with which it affects  the body. 

However, atypical antidepressants also affect the levels of dopamine, serotonin, and norepinephrine in the brain. 

Some of these drugs can cause abnormal heart rhythms that can be life threatening as well as cause a rare sexual disorder that involves painful and prolonged erection in males.

Some of these drugs are also not recommended in patients with active liver disease and it can increase the likelyhood of Suicidal thoughts or behavior. 

What are the uses of Antidepressants?

Antidepressants are primarily used to treat depression and depression related symptoms however, these medications are used not only to treat depression but for other conditions too.

Some of the conditions that these drugs have been approved for include:

  • agitation
  • obsessive-compulsive disorders (OCD)
  • childhood enuresis, or bedwetting
  • depression and major depressive disorder
  • generalised anxiety disorder
  • bipolar disorder
  • posttraumatic stress disorder (PTSD)
  • social anxiety disorder

Other “Off-Label” uses where the drug has not been approved for certain uses and conditions but tend to be effective include:

  • insomnia
  • pain
  • migraine


In this we tried to answer the question “Why does it take so long for antidepressants to work?”

We also discussed how long antidepressants take to work, and what can be done to improve the action of antidepressants as well as briefly discussed what antidepressants are.


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Cherney.L.What Medications Help Treat Depression?. Healthline. Retrieved on 8th February 2022. . https://www.healthline.com/health/depression/medication-list#atypical-medications

Depression Medications (Antidepressants). WebMD. Retrieved on  8th February 2022. https://www.webmd.com/depression/guide/depression-medications-antidepressants

Nordqvist.C. All about antidepressants. Medicalnewstoday. Retrieved on  8th February 2022. https://www.medicalnewstoday.com/articles/248320#uses

How Long Does it Take for Antidepressants to Work? The recovery village. Retrieved on 8th February 2022. https://www.therecoveryvillage.com/mental-health/depression/faq/how-long-for-antidepressants-to-work/#:~:text=Antidepressants%20take%20so%20long%20to,around%20to%20 experience%20pleasant%20 stimuli.

Why do antidepressants take so long to work? ScienceDaily. Retrieved on 8th February 2022. https://www.sciencedaily.com/releases/2016/07/160728125256.htm

Brogaard.B. Number One Reason SSRIs Take Four to Six Weeks to Work. Psychology Today. Retrieved on 8th February 2022. https://www.psychologytoday.com/us/blog/the-superhuman-mind/201702/number-one-reason-ssris-take-four-six-weeks-work

Samuel J. Erb, Jeffrey M. Schappi, Mark M. Rasenick. Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G protein, Gαs. Journal of Biological Chemistry, 2016; jbc.M116.727263 DOI: 10.1074/jbc.M116.727263

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