Take note that I am an occupational therapist and not a doctor.
Drugs (medication, just to be clear) are not my area of expertise. Therefore, I can’t give you any definitive advice regarding which antidepressant you should take, or whether you should take any at all.
This article simply serves to educate the audience to help make a better-informed decision based on facts, science, and statistics. ALWAYS consult with your primary care physician before taking antidepressants, since they can guide you through this process and give you valuable information!
That being said, I conducted a thorough review that highlighted certain medications that stand out in terms of both effectiveness and acceptability.
What are antidepressants?
Antidepressants are a class of medications primarily used to treat depression by affecting neurotransmitters (chemical messengers) in the brain. It influences hormones like serotonin, norepinephrine, and dopamine, which are all involved in regulating our mood. Multiple different types of antidepressants exist, each with its own particular possible side effects to varying degrees.
These drugs can also be prescribed for other mental health conditions at times, such as anxiety disorders, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and sometimes chronic pain.
Whether you should use antidepressants or not is up to you; they are often employed for severe depression, but can also be used for mild to moderate depression. I would advise you to always take medication if you’re severely depressed or at risk of harming yourself.
I can tell from personal experience that while the effects tend to wear off for me, they do help me function in the initial few months when depressed.
Are antidepressants safe?
Antidepressants are generally safe and effective for most people when prescribed and taken under a healthcare professional’s supervision.
However, like all medications, they can have side effects and risks.
The safety of antidepressants depends on several factors, such as:
- The specific type of medication you’re taking.
- The dosage.
- The individual’s medical history.
- Other drugs they may be taking.
I didn’t have any adverse consequences at all when I used antidepressants, and I’ve used 3 different types so far.
They aren’t one-size-fits-all, and the decision to start or continue antidepressant treatment should be made in close consultation with a healthcare provider who can properly assess the benefits and risks specific to your situation.
Here are the most common circumstances where you should be careful:
- Young people (under 25) and suicide risk
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- Increased suicidal thoughts
Antidepressants may increase the risk of suicidal thoughts and behaviors, particularly during the early weeks of treatment or when the dose is changed.
That’s especially true in children, teens, and young adults under 25. This is why close monitoring by a professional is essential during the initial treatment phase.
- Pregnancy and breastfeeding
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- Risk to the fetus
Some medications, especially certain SSRIs (e.g., Paxil), can increase the risk of birth defects when taken during pregnancy, particularly in the first trimester.
On the other hand, untreated depression can also pose risks to both the mother and the baby, so pregnant women should work with their doctor to find a safe treatment plan.
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- Breastfeeding
Some drugs can be passed to the baby through breast milk, which is why careful selection and monitoring are needed to minimize risks not only for the individual but for the baby as well.
- Bipolar disorder
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- Risk of triggering mania
People suffering from bipolar disorder can sometimes experience a shift from depression to mania when taking antidepressants. That risk is enhanced if they’re not taking a mood stabilizer.
Antidepressants should be prescribed cautiously and usually in combination with mood stabilizers like lithium or anticonvulsants in these specific cases.
- Heart conditions
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- Cardiovascular risks
They may not be safe for people with pre-existing heart conditions since they can increase the risk of heart attack, arrhythmias, or high blood pressure. At the very least, one should be cautious and consult with a doctor before employing such medications.
- Drug interactions
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- Serotonin syndrome
Taking antidepressants alongside other medications or supplements that increase serotonin levels (such as certain pain medications, migraine drugs, or St. John’s Wort) can lead to serotonin syndrome, a potentially life-threatening condition.
Symptoms include confusion, rapid heart rate, high blood pressure, and agitation.
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- Blood thinners
Some medications, especially SSRIs, can interact with blood thinners (e.g., warfarin or aspirin), increasing the risk of bleeding.
I used it together with oral minoxidil (which is also a vasodilator) and didn’t have any issues with it.
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- Other medications
There are cases of antidepressants interfering with medications to treat epilepsy, diabetes, or certain psychiatric conditions.
That’s why such instances require careful adjustment or alternative treatments at times.
- Severe liver or kidney disease
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- Slower metabolism
Something that not everyone might know is that antidepressants are processed by the liver and kidneys.
In individuals with liver or kidney disease, the body may not be able to clear the medication properly, leading to drug buildup and increased risk of side effects or toxicity.
- Alcohol or substance abuse
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- Compounded side effects
Combining antidepressants with alcohol or recreational drugs can have dangerous side effects like drowsiness, impaired coordination, or respiratory depression.
I drank the occasional pint when on antidepressants, and it didn’t affect me at all. However, it might be different for you, or if you drink large quantities.
Alcohol can also worsen depression and even make the medication less effective.
- Monoamine oxidase inhibitor (MAOI) precautions
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- Food and drug interactions
MAOIs are a less commonly prescribed class of antidepressants.
One of the reasons is that they can cause dangerous spikes in blood pressure if taken with certain foods (like those rich in tyramine, cheese, and smoked meats) or other medications.
These require strict dietary restrictions and careful monitoring because of the potential dangers when misused or abused.
- Allergic reactions
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- Allergy to medication
Though rare, some people may have an allergic reaction to certain antidepressants.
Symptoms can include rash, itching, and swelling, but also more serious conditions like difficulty breathing or anaphylaxis.
ALWAYS consult a doctor as quickly as possible when you have severe issues, such as difficulty breathing, since that can potentially be life-threatening.
- Seizure disorders
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- Lowered seizure threshold
Certain antidepressants, such as bupropion (Wellbutrin), can lower the seizure threshold, meaning they may increase the risk of seizures in individuals who are prone to them.
This is especially a concern at higher doses or for individuals with a history of seizures.
- Sudden discontinuation
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- Withdrawal or discontinuation syndrome
Suddenly stopping or rapidly reducing the dose of antidepressants, particularly SSRIs and SNRIs, can lead to withdrawal-like symptoms (headaches, dizziness, irritability, flu-like symptoms).
This is why gradual tapering under medical supervision is recommended when discontinuing treatment to ensure it goes smoothly and without problems.
- Elderly individuals
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- Increased sensitivity to side effects
Older adults may be more sensitive to certain side effects of antidepressants, like confusion, falls, or other cognitive issues.
Some types of antidepressants, such as tricyclic antidepressants (TCAs), are often avoided in older adults because of these dangers.
- Severe or untreated glaucoma
Certain antidepressants, especially Tricyclic Antidepressants (TCAs) and some SNRIs, can increase intraocular pressure, worsening narrow-angle glaucoma.
This can lead to severe eye pain and vision issues.
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- Monoamine oxidase inhibitors (MAOIs)
MAOIs are also contraindicated in individuals with glaucoma due to potential increases in intraocular pressure.
- Pheochromocytoma
This is a rare tumor of the adrenal gland that can cause dangerously high blood pressure.
Antidepressants such as SNRIs (which affect norepinephrine levels) and MAOIs can worsen existing blood pressure issues and lead to hypertensive crises in people with this condition.
- Hyperthyroidism or uncontrolled thyroid disorders
Antidepressants that influence norepinephrine (like SNRIs or TCAs) can increase heart rate and blood pressure and may worsen symptoms in people with hyperthyroidism.
In cases where the thyroid is overactive, medications that stimulate the central nervous system may not be safe.
- History of stroke or vascular disorders
Some medications like SNRIs and TCAs can affect blood pressure or vascular tone and may not be safe for people with a history of stroke (CVA) or transient ischemic attacks (TIAs).
The hazards of increasing blood pressure or causing vascular complications might outweigh the benefits in these specific instances.
- Severe hypertension (high blood pressure)
SNRIs (e.g., venlafaxine) and TCAs may raise blood pressure in some individuals.
These types of antidepressants may be contraindicated for those with uncontrolled hypertension since they can increase the risk of heart attacks, strokes, or going through other cardiovascular events.
- Prostate enlargement (benign prostatic hyperplasia – BPH)
Some antidepressants, like TCAs and medications with anticholinergic properties, can cause urinary retention and make it difficult for men with enlarged prostates to urinate.
This can worsen BPH symptoms and cause discomfort or more serious urinary issues.
- Bleeding disorders or high risk of bleeding
SSRIs and SNRIs can increase the danger of bleeding.
That’s why individuals who take blood thinners (e.g., warfarin or aspirin) or have a history of gastrointestinal bleeding should take caution.
This risk is due to these antidepressants on platelet function. In these cases, alternative treatments or closer monitoring may be necessary to guarantee the user’s safety.
- Parkinson’s disease
There are antidepressants like TCAs, for instance, that can worsen symptoms of Parkinson’s disease by interfering with dopamine function or causing anticholinergic side effects (like confusion or motor control issues).
Dopaminergic antidepressants, such as bupropion, can be a better option in these circumstances but still require caution and monitoring.
- Porphyria
Porphyria is a rare metabolic disorder.
Certain medications like MAOIs and some TCAs can exacerbate it.
These drugs can trigger attacks in individuals with the illness, leading to abdominal pain, neuropathy, and mental health changes.
- Severe cognitive impairment or dementia
TCAs and anticholinergic antidepressants can cause confusion, memory problems, and worsen cognitive impairment in older adults or people with dementia.
These medications can indirectly increase the risk of falls, delirium, and a decline in mental function, making them less suitable for the aging population and those who are suffering from some kind of cognitive issues.
- Metabolic syndrome or obesity
This can exacerbate health risks in people who already have obesity or metabolic syndrome (a cluster of conditions including high blood pressure, high blood sugar, and abnormal cholesterol levels).
- Recent myocardial infarction (heart attack)
TCAs and some SNRIs should generally be avoided immediately following a heart attack because they can affect heart rhythm, increase heart rate, or raise blood pressure.
This can be dangerous in this vulnerable period after a heart attack, since the heart is weakened and needs time to recover after this occurrence.
- Psychotic depression
In cases of psychotic depression, where depression is accompanied by psychosis (e.g., delusions or hallucinations), antidepressants alone may be contraindicated.
A combination of antipsychotic medications and antidepressants is typically recommended in these instances, as antidepressants alone can worsen psychotic symptoms.
- Hypertensive crisis with MAOIs
MAOIs can cause severe and dangerous increases in blood pressure, also known as hypertensive crises, if combined with certain foods (like those containing tyramine) or medications (such as decongestants, stimulants, or other antidepressants).
MAOIs are generally contraindicated in people who may struggle to follow the necessary dietary and medication restrictions because of these potentially dangerous interactions.
Should you take antidepressants?
Deciding whether to use antidepressants is a major and personal choice.
I believe that it’s best made in consultation with your primary healthcare physician, doctor, or psychiatrist.
Although I would say that it’s almost a no-brainer if you’re suicidal or so severely depressed that you can’t function anymore due to the severity of the symptoms. If that’s the case, then I believe it’s always worth employing the help of medication.
There are several factors to consider when evaluating whether antidepressants might be helpful for you specifically:
- Severity of symptoms
Mild depression can usually be treated without medication, although it can still be useful.
Lifestyle changes, therapy, or short-term interventions might be enough to improve mood without the use of drugs.
Antidepressants are probably recommended if you’re suffering from moderate to severe depression. That’s particularly true if the symptoms significantly impair your daily functioning or quality of life.
Speaking from personal experience, using antidepressants was useful, especially in the beginning, although the effects tapered off after a couple of months. But that might not be the case for you, and they might continue to work.
- Duration of depression
Because in my opinion, what do you have to lose at that point? It should at least deserve some consideration.
- Other treatments
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- Therapy
Cognitive behavioral therapy (CBT), counseling, and other forms of therapy are highly effective and should be tried before or alongside medication.
CBT made a very positive change in my life and helped me adjust my negative thinking while helping me establish healthy (sustainable) lifestyle habits.
Healthy lifestyle changes such as regular exercise, a balanced diet, sufficient sleep, and practicing relaxation can also positively impact mood while being low-entry, low-cost pieces of the treatment puzzle.
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- Combined treatment
Most people experience the best results from using antidepressants alongside therapy.
That comes as no surprise, since therapy is usually needed to address the root cause of the issue that’s causing the psychological problem.
- Potential benefits
Whether someone should employ the aid of medication is always a cost-benefit analysis.
Antidepressants can alleviate symptoms such as insomnia, low mood, lack of motivation, and anxiety.
They’re life-changing for some, restoring a sense of normalcy after struggling with depression. For others, they don’t do much, if anything at all. Everyone is different, and that means that it’s hard to decide if it will be beneficial for you or not without trying.
Some people experience no or only minimal side effects, while others need to try multiple different medications to find the right fit that they can tolerate.
- Long-term commitment
Antidepressants usually take 4–6 weeks to start showing effects and may need to be taken for several months or longer, depending on the person.
That seems about right, seeing as it took me a couple of weeks before I started to notice positive effects of the antidepressants when I was taking them.
Discontinuing antidepressants should always be done under medical supervision to avoid going through symptoms of withdrawal or potentially relapsing.
- Risk of dependency
- Personal and family history
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- Previous experience with antidepressants
If you’ve used them in the past, and they were helpful, then it’s probably more likely that a doctor would suggest them again since they worked before.
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- Family history
If a close relative has responded well to a specific type of antidepressant, this information might guide your doctor’s decision to advise you to try medication.
That’s because genetic factors can also influence how people respond to medications.
- Underlying health conditions
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- Chronic conditions
When you’re suffering from other physical or mental health issues, antidepressants may be prescribed as part of a broader treatment plan.
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- Pregnancy and breastfeeding
Some antidepressants can be more appropriate than others if you’re pregnant or planning to conceive, since certain drugs can affect the fetus or infant.
Again, talk to a professional healthcare professional since they can give you the best advice before deciding.
- Co-occurring mental health conditions
Antidepressants can sometimes be part of a larger pharmacological approach, but your doctor might be cautious about prescribing the correct type out of fear that it might cause the worsening of one of your preexisting illnesses.
For example, avoiding antidepressants that have the possibility of triggering mania in bipolar disorder.
- Your current medication regimen
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- Drug interactions
Your doctor will assess whether an antidepressant could interfere with the medications you’re already taking.
- Personal preferences
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- Comfort with medication
Some people prefer to avoid taking medication whenever possible, while others are more open to pharmacological treatment.
Even though I’m not a big fan of taking medicine when it can be helped, I’ll admit that it did help me, and that it’s absolutely necessary in some cases, especially when suicidal or at risk for self-harm.
If you have doubts about taking antidepressants, then it’s best to discuss these concerns with your doctor, since they can help guide the decision.
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- Natural or holistic approaches
People can prefer to explore complementary treatments like herbal remedies, supplements, or alternative therapies like acupuncture or yoga.
These might be used together with or in place of medication, depending on the individual’s goals.
- Cost and access
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- Affordability
While many antidepressants can be cost-effective while being available as generics, the affordability and insurance coverage of certain drugs may influence your decision.
At the end of the day, we all get bills to pay. Still, your health is worth investing in!
Medication might be a more accessible first line of treatment if you don’t have regular access to therapy or other mental health resources.
Nevertheless, it’s ideally combined with some form of support. Be it informal support in the form of friends and family, or formal assistance by professionals.
- Time to commitment
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- Delayed onset
Antidepressants often take several weeks to show their full effects. During this time, symptoms might not improve and could even get slightly worse in the beginning.
This period can be challenging, and it’s important to be patient and stay in close communication with your doctor during the first few months for additional support and to figure out if changes are needed in your regimen.
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- Commitment to trial and error
Finding the right antidepressant may require trying more than one type of medication, adjusting doses, and combining treatments.
This trial-and-error process can take time, but it’s necessary to find what works best for you.
- Risk of suicide (Especially in younger people)
Some antidepressants have been associated with a slightly increased risk of suicidal thoughts and behaviors, especially in the first few weeks of treatment. That’s particularly true for younger adults and teenagers.
This risk is small, but it’s nonetheless something your doctor will carefully monitor if antidepressants are prescribed.
- Lifestyle factors
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- Substance use
Regularly using alcohol or recreational drugs can interfere with the effectiveness of antidepressants or increase side effects.
I did drink occasionally (although not to the point of getting wasted) when using antidepressants, and personally didn’t notice any adverse consequences.
Your physician may address this before or alongside medication treatment.
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- Stress levels and external environment
Life events can contribute to depression. Think of instances like job stress, relationship issues, or financial difficulties.
Sometimes, addressing these external factors with or without medication can help improve temperament.
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- Older adults
Older folks may have different responses to antidepressants.
Thus, their medication needs can vary due to the presence of other conditions or medications.
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- Children and adolescents
Antidepressants are generally prescribed with caution in younger populations, and treatment typically includes therapy.
But in my opinion, therapy should always be included as part of the solution. Rarely does medication cure the root cause of depression.
Potential side effects of antidepressants
As established at the start of this post, antidepressants are generally safe and well-tolerated.
While they can be highly effective, they may also cause aftereffects, which vary depending on the type of antidepressant, the individual taking it, and the dosage.
Most of these complications will be harmless, but there are a few rare ones to look out for since they can be dangerous.
Let’s look at potential side effects, categorized by class of antidepressants:
Common examples: Fluoxetine (Prozac), Sertraline (Zoloft), Escitalopram (Lexapro), Paroxetine (Paxil), and Citalopram (Celexa).
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- Common side effects
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- Nausea.
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- Diarrhea or constipation.
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- Drowsiness or insomnia.
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- Dry mouth.
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- Weight gain or loss.
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- Reduced sexual desire or performance (erectile dysfunction or delayed orgasm).
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- Increased sweating.
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- Nervousness or agitation.
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- Dizziness.
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- Rare side effects (but potentially dangerous)
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- Bruising or bleeding easily (rare but serious).
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- Serotonin syndrome (symptoms include confusion, rapid heart rate, and high blood pressure when serotonin levels are excessive).
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Common examples: Venlafaxine (Effexor), Duloxetine (Cymbalta), Desvenlafaxine (Pristiq).
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- Common side effects
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- Nausea.
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- Dry mouth.
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- Fatigue.
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- Increased sweating.
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- Constipation.
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- Insomnia.
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- Loss of appetite.
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- Rare side effects
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- Increased blood pressure (especially with higher doses).
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- Sexual dysfunction.
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- Risk of serotonin syndrome.
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Common examples: Amitriptyline, Nortriptyline (Pamelor), Imipramine (Tofranil).
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- Common side effects
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- Drowsiness.
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- Dry mouth.
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- Blurred vision.
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- Constipation.
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- Dizziness.
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- Weight gain.
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- Rare side effects
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- Heart rhythm disturbances.
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- Low blood pressure upon standing (orthostatic hypotension).
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- Urinary retention.
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- Caution
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- TCAs can be toxic in overdose situations!
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Common examples: Phenelzine (Nardil), Tranylcypromine (Parnate), Isocarboxazid (Marplan).
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- Common side effects
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- Dizziness.
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- Drowsiness.
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- Insomnia.
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- Dry mouth.
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- Weight gain.
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- Nausea.
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- Serious risks
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- Hypertensive crisis
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This can happen if taken with foods high in tyramine, such as aged cheese, cured meats, or certain medications.
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- Interaction with other drugs
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Interaction with other drugs, including SSRIs and SNRIs, may lead to serotonin syndrome.
Common examples: Bupropion (Wellbutrin), Mirtazapine (Remeron), Trazodone.
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- Common side effects
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- Insomnia.
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- Dry mouth.
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- Weight loss.
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- Agitation.
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- Headaches.
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- Rare risks
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- Seizures (at high doses or with predisposing factors).
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- Common side effects
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- Sedation (often used for insomnia).
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- Weight gain.
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- Increased appetite.
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- Less common side effects
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- Dizziness.
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- Dry mouth.
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- Common side effects
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- Sedation.
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- Dizziness.
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- Dry mouth.
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- Nausea.
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- Rare risks
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- Priapism (a prolonged and painful erection).
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Common examples: Vilazodone (Viibryd), Vortioxetine (Trintellix).
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- Common side effects
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- Nausea.
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- Diarrhea.
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- Dizziness.
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- Insomnia or drowsiness.
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- Reduced sexual function (less than SSRIs/SNRIs).
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General considerations
- Initial side effects
Many common side effects, such as nausea or insomnia, improve after the first few weeks as the body adjusts to the medication.
Abruptly stopping antidepressants, especially SSRIs or SNRIs, could cause withdrawal-like symptoms like dizziness, irritability, and flu-like symptoms.
Always taper off under medical guidance.
All antidepressants carry a warning for an increased risk of suicidal thoughts and behaviors, particularly in children, adolescents, and young adults under 25.
Certain antidepressants, such as SSRIs and SNRIs, are more dangerous and prone to increase the risk of suicide.
Possible psychological side effects
Some individuals feel less emotionally responsive or “numb.”
A temporary increase in anxiety or restlessness, notably during the first few weeks of treatment.
Antidepressants can trigger mania or hypomania in people with bipolar disorder in some exceptional instances.
A rare feeling of being detached from reality or oneself.
Potential neurological side effects
These mostly occur during the initial adjustment period.
Some antidepressants, especially SSRIs and SNRIs, can cause involuntary movements.
Medications like Bupropion carry a higher risk at high doses or in people predisposed to seizures.
Rare cases of tardive dyskinesia (involuntary facial or body movements) or akathisia (a sense of restlessness) have been reported by some people.
Hormonal and endocrine effects
Low sodium concentrations are more common in older adults and people taking SSRIs or SNRIs.
Symptoms include confusion, fatigue, and muscle weakness.
Antidepressants may affect glucose regulation.
This happens more frequently in people with diabetes.
Some medications, like certain TCAs or antipsychotics combined with antidepressants, raise prolactin levels.
This can cause menstrual irregularities or breast tenderness.
Gastrointestinal effects
Antidepressants can increase stomach acid production.
Though less common, they can occur alongside nausea and diarrhea.
Some people experience irregular hunger or cravings beyond simple weight gain or loss.
Cardiovascular effects
Some antidepressants, like Citalopram and Amitriptyline, could lead to heart rhythm issues in susceptible individuals.
A sensation of skipped or racing heartbeats.
A sudden drop in blood pressure when standing.
This happens more frequently with TCAs and MAOIs.
Sexual side effects (beyond the common ones)
This stands for the inability to reach an orgasm, even with adequate stimulation.
Some people report numbness or decreased sensitivity in the genital area.
Sexual side effects sometimes persist even after discontinuing the medication.
Dermatological effects
Mild rashes or severe reactions (Stevens-Johnson Syndrome) are unusual but possible.
Increased sensitivity to sunlight, which happens more regularly with certain TCAs and MAOIs.
Some report thinning hair or increased shedding.
Immunological and rare systemic effects
Some antidepressants may slightly suppress immune function, though the evidence is limited.
Uncommon but can appear with medications like Nefazodone (no longer widely used due to this risk).
Certain antidepressants could affect kidney health in older adults or those with preexisting conditions.
Uncommon behavioral and cognitive side effects
Increased impulsive behaviors, such as gambling or making risky decisions.
Temporary cognitive difficulties or forgetfulness.
Mostly happens with medications like Trazodone or TCAs.
Withdrawal and discontinuation symptoms
When stopping antidepressants, especially abruptly, individuals may experience:
- Brain “zaps” (electric shock-like sensations in the head).
- Flu-like symptoms (fatigue and muscle aches).
- Rebound anxiety or depression.
Diverse side effects
An oddly specific but reported side effect of SSRIs.
Some individuals report altered taste sensations.
Edema in the hands, feet, or ankles.
Rare and severe complications
An uncommon but life-threatening condition with symptoms like fever, muscle rigidity, and confusion.
A severe allergic reaction that causes widespread inflammation.
What to do about side effects?
- Communicate with your doctor
Many side effects can be managed by adjusting the dose, timing, or switching medications.
- Lifestyle adjustments
For instance, taking medicines with food to reduce nausea, and exercising to counter weight gain.
- Monitor for serious symptoms
Seek immediate medical attention if you experience symptoms like severe allergic reactions, chest pain, or serotonin syndrome.
These can be dangerous, which is why you shouldn’t wait to receive medical attention. Make sure to quit your antidepressants instantly if you do happen to go through these aftereffects.
What are the different types of antidepressants?
There are several different types of antidepressants, each affecting brain chemistry in different ways.
These are the main categories:
- Selective serotonin reuptake inhibitors (SSRIs)
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- How they work:
SSRIs increase the levels of serotonin in the brain by blocking its reabsorption (reuptake).
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- Examples:
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- Fluoxetine (Prozac).
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- Sertraline (Zoloft).
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- Escitalopram (Lexapro).
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- Serotonin-norepinephrine reuptake inhibitors (SNRIs)
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- How they work:
Boost the levels of both serotonin and norepinephrine by preventing their resorption.
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- Examples:
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- Venlafaxine (Effexor).
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- Duloxetine (Cymbalta).
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- Tricyclic antidepressants (TCAs)
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- How they work:
They block the reuptake of the neurotransmitters serotonin and norepinephrine. Unfortunately, they are older and often have more side effects.
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- Examples:
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- Amitriptyline.
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- Nortriptyline (Pamelor).
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- Monoamine oxidase inhibitors (MAOIs)
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- How they work:
MAOIs work by inhibiting the enzyme monoamine oxidase, which breaks down serotonin, norepinephrine, and dopamine.
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- Examples:
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- Phenelzine (Nardil).
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- Tranylcypromine (Parnate).
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- Note:
MAOIs can have serious interactions with certain foods and medications.
- Atypical antidepressants
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- How they work:
These don’t fit into the other categories and have unique mechanisms of action.
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- Examples:
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- Bupropion (Wellbutrin).
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- Mirtazapine (Remeron).
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- Trazodone.
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There are a few additional types of antidepressants that I purposely didn’t include in the initial list.
That’s because these are newer or less commonly used medications, but that does in no way mean they’re any less viable for treating psychological issues. Although, as always, there can be some risks.
These novel drugs are:
- Serotonin modulators
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- How they work:
They can enhance serotonin activity in some areas while suppressing it in others, depending on what’s needed to treat the issue.
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- Examples:
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- Vilazodone (Viibryd): Works as a selective serotonin reuptake inhibitor (like SSRIs) but also acts as a partial agonist of serotonin receptors.
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- Vortioxetine (Trintellix): Influences multiple serotonin receptors and reuptake, affecting the serotonin system more broadly than SSRIs.
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- Norepinephrine-dopamine reuptake Inhibitors (NDRIs)
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- How they work:
These obstruct the reabsorption of both norepinephrine and dopamine, rather than serotonin.
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- Example:
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- Bupropion (Wellbutrin): Often used to treat depression and as an aid to stop smoking. It’s unique because it typically doesn’t cause sexual side effects or weight gain like many other antidepressants.
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- Tetracyclic antidepressants
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- How they work:
These drugs work similarly to tricyclic antidepressants, but have a different chemical structure. They also impact the norepinephrine and serotonin levels and regularly act as antagonists at certain receptors.
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- Example:
- NMDA receptor antagonists (Ketamine-like antidepressants)
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- How they work:
NMDA receptor antagonists act on the glutamate system by blocking the NMDA receptors. They are usually used for treatment-resistant depression.
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- Examples:
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- Esketamine (Spravato): A nasal spray version of ketamine, approved for treatment-resistant depression.
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- Ketamine: Typically used off-label for depression in clinical settings.
It can have rapid, positive short-term effects on depressive symptoms.
- Ketamine: Typically used off-label for depression in clinical settings.
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- 5-HT2 receptor antagonists
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- How they work:
They block serotonin (5-HT2) receptors, which can help alleviate depression and anxiety.
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- Example:
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- Trazodone is frequently used for its sedating effects as well as for depression.
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- Agomelatine
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- How it works:
This drug acts as an agonist at melatonin receptors and an antagonist at serotonin receptors. It works by regulating the circadian rhythm and improving sleep quality, which helps to stabilize mood.
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- Example:
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- Agomelatine (Valdoxan): Mainly employed in Europe and other regions outside the U.S.
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These newer or atypical antidepressants target different neurotransmitter systems and are often prescribed when traditional SSRIs or SNRIs aren’t effective or well-tolerated.
How long do antidepressants take to work?
It usually takes several weeks (often 4–6 weeks) before antidepressants begin to show their full effects.
For me, it took about 5 weeks before I started noticing any consequences, such as improved mood and better sleep.
It’s common for doctors to start with a low dose and gradually increase it since it takes some time before they show their effect, and because they want to keep the efficacious dose as low as possible.
What are the most effective antidepressants for managing depression?
Medication isn’t always necessary to treat depression. But it’s typically used and required for serious depression or when the person is at risk for self-harm.
Selecting the most effective antidepressant involves considering both efficacy and individual patient factors.
Notable antidepressants:
This tricyclic antidepressant has been shown to more than double the chances of treatment response compared to placebo, making it one of the most effective options.
Escitalopram has demonstrated superior efficacy and acceptability among selective serotonin reuptake inhibitors (SSRIs).
Mirtazapine is known for its rapid onset of action and is considered effective, especially in cases where sleep disturbances are prominent.
This serotonin-norepinephrine reuptake inhibitor (SNRI) has shown higher effectiveness compared to some SSRIs, though it may come with a different side effect profile.
Recognized for its efficacy and favorable tolerability, vortioxetine is another viable option for treating major depressive disorder.
Most effective classes of antidepressants:
- Selective serotonin reuptake inhibitors (SSRIs)
These are commonly used as first-line treatments due to their effectiveness and relatively mild side effects.
Regularly used for major depressive disorder (MDD) and anxiety disorders. It has a well-established safety profile.
One of the most widely prescribed SSRIs, which is known for its long half-life, makes withdrawal symptoms less severe.
Effective but associated with more withdrawal symptoms and potential weight gain.
Similar to escitalopram but may have a slightly higher risk of QT prolongation (heart rhythm issues).
- Serotonin-norepinephrine reuptake inhibitors (SNRIs)
SNRIs work by increasing serotonin and norepinephrine levels in the brain.
Effective for both depression and chronic pain conditions like fibromyalgia.
A newer SNRI that’s similar to venlafaxine but with fewer drug interactions.
Approved for MDD, with a more balanced effect on serotonin and norepinephrine.
- Atypical antidepressants
These medications work differently from SSRIs or SNRIs.
A norepinephrine-dopamine reuptake inhibitor (NDRI).
It does not cause sexual dysfunction or weight gain like some SSRIs, but may increase anxiety in some individuals.
Primarily used as a sleep aid, but also has antidepressant properties.
Comparable to trazodone but with a lower risk of drowsiness. However, it has a rare risk of liver toxicity.
A serotonin modulator with both SSRI and partial agonist effects, possibly reducing sexual side effects.
Works on melatonin receptors and serotonin receptors, making it potentially helpful for depression with sleep disturbances.
- Tricyclic antidepressants (TCAs)
These older antidepressants are effective, but with more side effects.
Has fewer side effects than other TCAs but still requires careful monitoring.
Effective for severe depression but associated with strong anticholinergic side effects.
Often used at low doses for insomnia, but also manages depression.
- Monoamine oxidase inhibitors (MAOIs)
These are typically used when other antidepressants fail due to dietary restrictions and interactions.
Effective but requires dietary restrictions to avoid hypertensive crises.
Another MAOI with stimulating effects but similar dietary restrictions.
Available as a transdermal patch, which reduces dietary restrictions compared to oral MAOIs.
- Newer and experimental antidepressants
A nasal spray version of ketamine that’s used for treatment-resistant depression.
A dissociative anesthetic that has rapid-acting antidepressant effects, particularly for suicidal patients.
Approved for postpartum depression that works on GABA receptors.
Being studied for its rapid antidepressant effects in treatment-resistant depression.
While SSRIs and SNRIs are generally the first-line choices due to their safety profiles, other options like bupropion, mirtazapine, and TCAs can be more effective depending on the individual.
MAOIs and newer treatments like ketamine or esketamine are reserved for more severe, treatment-resistant cases.
Additional but less common antidepressants:
- Serotonin modulators and stimulators (SMS)
These pills work by modulating serotonin activity in a different way than SSRIs.
A unique antidepressant that ironically enhances serotonin reuptake rather than inhibiting it.
It has anxiolytic (anti-anxiety) properties and is sometimes used for mild-to-moderate depression.
Has anxiolytic and antidepressant effects similar to TCAs but with a lower side effect profile.
It’s used mainly in Europe.
- Noradrenergic and specific serotonergic antidepressants (NaSSAs)
These target norepinephrine and serotonin differently from SSRIs.
An antidepressant akin to mirtazapine but with a different chemical structure.
- Triple reuptake inhibitors (TRIs) – experimental and emerging treatments!
These drugs inhibit serotonin, norepinephrine, and dopamine reuptake.
Initially studied for obesity, it has shown potential as an antidepressant due to its impact on all three major monoamines.
A TRI that is investigated for depression and ADHD, but not yet widely used clinically.
- Glutamatergic agents
These work on glutamate rather than serotonin or norepinephrine.
An NMDA receptor modulator like ketamine that has shown promise for rapid antidepressant effects without dissociation.
It was originally used for tuberculosis but has shown some antidepressant effects in small studies.
- Anti-inflammatory and hormonal approaches
An antibiotic with anti-inflammatory properties that has been studied for depression, particularly in cases with neuroinflammation.
A hormone that may sometimes help with mood disorders.
- Tricyclic and tetracyclic antidepressants (TCAs and TeCAs)
A tetracyclic antidepressant that primarily acts on norepinephrine and is used for major depressive disorders, but with a higher risk of side effects.
A less sedating TCA that’s sometimes used for depression with extreme fatigue.
- Monoamine oxidase inhibitors (MAOIs) – less commonly used
Another MAOI that can be applicable in severe depression, but requires dietary restrictions.
A reversible MAOI (RIMA) that’s used in some countries and has fewer dietary restrictions compared to traditional MAOIs.
- Glutamatergic and neurosteroid-based antidepressants
Akin to ketamine but designed to lower dissociative side effects.
A neurosteroid that’s currently being studied for its antidepressant properties by working on GABA receptors.
- Cholinergic and histaminergic modulators
Traditionally used for motion sickness, but has rapid-acting antidepressant effects in some studies.
Mainly used for vertigo, but has since been explored for its potential antidepressant effects.
- Serotonergic antidepressants with unique mechanisms
While primarily an antipsychotic, low-dose amisulpride has antidepressant effects by enhancing dopamine activity.
A combination of an SSRI (fluoxetine) and an atypical antipsychotic (olanzapine) can be used for treatment-resistant depression and bipolar depression.
Take note that the antidepressants mentioned above are either used in specific cases or are emerging as potential treatments.
If you’re looking for well-established alternatives, amisulpride (low dose), isocarboxazid, and maprotiline may be useful options.
Glutamatergic agents like rapastinel and tesofensine are promising if you’re looking for newer or experimental options.
Otherwise, older but less common antidepressants like tianeptine and opipramol can be helpful alternatives.
Individual response and side effects:
Individual responses to antidepressants can vary. That’s also why it’s so difficult to determine one medication that’s best for each person, since everyone differs.
Factors such as genetics, co-existing medical conditions, and potential drug interactions play major roles in determining the most suitable medication.
While the antidepressants mentioned above have demonstrated efficacy, they also come with possible side effects.
For instance:
May cause drowsiness, weight gain, and anticholinergic effects like dry mouth and constipation.
Common side effects include nausea, sexual dysfunction, and insomnia.
It could lead to increased blood pressure, especially at higher doses, and may cause withdrawal symptoms if discontinued abruptly.
Guidelines and recommendations
However, the choice of antidepressant should be individualized by considering the patient’s preferences, previous treatment responses, and specific symptom profiles.
Final note
Antidepressants are medications designed to help relieve symptoms of depression by balancing brain chemicals linked to mood and emotion.
They’re not a quick fix or a cure, but for many people, they’re a valuable part of treatment, often used alongside therapy and lifestyle changes to support long-term recovery.
Since antidepressants or any medication for that matter is not my area of expertise, you should always talk with a doctor before starting to use them. That will make sure that you have someone knowledgeable in the field to guide you and adjust the dosages if necessary.
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