Antidepressant drugs – shocking revelation
- What are antidepressants meaning?
- How many antidepressant types?
- 1. TCA’s (Tricyclic antidepressants)
- 2. SNRI’s (Serotonin Norepinephrine Reuptake Inhibitors)
- 3. SSRI’s (Selective Serotonin Reuptake Inhibitors)
- 4. MAOI’s (Monoamine Oxidase inhibitors)
- 5. Atypical antidepressants
- How do antidepressants work?
- What is the most commonly prescribed antidepressant?
- Do antidepressant drugs have side effects?
- Are antidepressant drugs safe in pregnancy?
- Which medicines should not be taken with antidepressant drugs?
- Is Antidepressant drugs a life-long treatment?
In my last post, I explained about signs of depression. Today, in this post, we will talk about antidepressant drugs.
There are a lot of myths and common misconception behind antidepressant drugs like
Antidepressant drugs do not work…
They have horrible side effects…
Antidepressants are addictive…
These drugs have lifelong treatment…
Well, I will provide you with complete information about antidepressant drugs with scientific evidence.
Let’s go ahead towards the topic and understand with basics.
What are antidepressants meaning?
Antidepressants are the drugs that help you in the treatment of depression and other mental disorders. These drugs enhance your mood in depressive illness.
It controls the imbalanced chemicals in your neuron.
Antidepressants help to relieve signs of depression and make the depression go away.
These drugs make you feel better, improves the quality of life, and provide the strength you to face social environmental issues.
How many antidepressant types?
Antidepressant medicines are divided into several categories based on the mechanism of action. The classes of antidepressants are –
1. TCA’s (Tricyclic antidepressants)
Tricyclic antidepressants are the drug of choice in severe depression like major depressive disorder (MDD) because of their high efficacy.
TCA’s are first-generation antidepressants.
TCA’s are also used in the off-label like neuropathic pain, headache, migraine, fibromyalgia, gastrointestinal syndromes, pelvic pain, insomnia, and other psychiatric conditions.
It includes –
NA + Serotonin reuptake inhibitors
Trimipramine, Doxepin, Dothiepin and Clomipramine
Mostly NA reuptake inhibitors
Desipramine, Nortriptyline, Protriptyline, Amoxapine, Reboxetine, Maprotiline.
2. SNRI’s (Serotonin Norepinephrine Reuptake Inhibitors)
SNRI’s/SSRI’s are second-generation antidepressants as more selective action on monoamines.
It is given to those patients who are ineffective from SSRIs. Sometimes it is effective in neurological pain like – diabetic peripheral neuropathy.
It includes –
Venlafaxine and Desvenlafaxine.
3. SSRI’s (Selective Serotonin Reuptake Inhibitors)
They are a drug of choice in mild to moderate depression because of high safety concerns.
SSRIs have 300 to 3000-fold greater selectivity for the serotonin transporter.
SSRI’s antidepressants examples include –
Fluvoxamine, Dapoxetine, and Citalopram.
4. MAOI’s (Monoamine Oxidase inhibitors)
MAOIs have infrequently prescribed medicines as it is reported a higher incidence of drug-drug and drug-food interaction, especially with cheese foods.
These drugs are also first-generation antidepressants.
Isocarboxazid, phenelzine, selegiline (in patch form), tranylcypromine
These are a newer generation of drugs. They are not much efficacious than TCA’s and SNRI’s but they have fewer side effects. This group includes –
Tianeptine, Amineptine, Trazodone, and Mianserin.
How do antidepressants work?
Let’s understand by stepwise –
Synthesis of neurotransmitters –
As we know, whatever we eat protein in our daily life, they get converted into various amino acids.
Among these, tyrosine amino acid goes to neurons, and the rest are distributed to other body parts.
That tyrosine goes inside the synaptic knob (axon terminal) by the transporter which presents at the outer membrane of a synaptic knob.
Dopamine travel into synaptic vesicles (store various neurotransmitters) by pump – vesicular monoamine transporter
If dopamine release, there is an absence of dopamine beta-hydroxylase.
If norepinephrine release, there is a presence of dopamine beta-hydroxylase.
There are few synaptobrevin proteins present at the integral membrane of synaptic vesicles which fuse to syntaxins protein present at presynaptic membrane then exocytosis takes place and eventually, neurotransmitters release.
These neurotransmitters act on their target organs and some reuptake or reabsorb into synapse by reuptake-1 (neuronal uptake) and synaptic vesicle by reuptake-2 (vesicular uptake).
Some neurotransmitters are degraded by MAO (monoamine oxidase) enzyme which is present at mitochondria in a synaptic knob.
Likewise, serotonin synthesis by tryptophan amino acid
Store into synaptic vesicles in the form of 5-hydroxytryptamine (Serotonin).
The excess accumulation of neurotransmitters increases the osmotic pressure in vesicles and it may automatically burst.
To prevent this burst, neurotransmitters complex with some neuroendocrine secretory proteins called chromogranin, ATP, and some ascorbic acids.
In depression – All these monoamines neurotransmitters (serotonin, dopamine, and neurotransmitter) decrease in the condition of depression.
Antidepressant drugs –
Antidepressant drugs enhance the concentration of these neurotransmitters by inhibiting the reuptake of monoamines (serotonin, dopamine, and norepinephrine).
1. TCA’s – These classes of drugs increase the level of norepinephrine and serotonin by block the neuronal uptake into the presynaptic nerve terminal.
They have little activity on blockage of muscarinic, histamine, and adrenergic receptors.
2. SNRI’s – They enhance the level of norepinephrine and serotonin by block the neuronal uptake into the presynaptic nerve terminal.
3. SSRI’s – These drugs only increase the level of serotonin by specifically inhibit serotonin reuptake that’s why it is called selective serotonin reuptake inhibitors.
4. MAOI’s – These drugs inhibit the monoamine oxidase enzyme and prevent the degradation of neurotransmitters. This result increased the store of norepinephrine, dopamine, and serotonin in synaptic vesicles.
5. Atypical antidepressants – They have a mixed group of agents which increase the level of serotonin, dopamine, and norepinephrine.
What is the most commonly prescribed antidepressant?
As per an Indian study, SSRI and citalopram are the most common medications prescribed in depression among all antidepressants.
The psychiatrist or other physician generally start the treatment with these class of drugs.
These drugs have good efficacy and well tolerability. As far as the concern about safety, they have the least side effects than other antidepressants.
These drugs have good absorption in the systemic circulation.
Do antidepressant drugs have side effects?
Every medicine has desirable effects and undesirable effects. Like all medicines, antidepressants also have side effects although not everybody gets them.
Most of the antidepressants have few common side effects like
- Gastric disturbances
- Weight gain (a classical example is Mirtazapine)
- Reduced sexual performance
Well, I have some mnemonic to remember antidepressant side effects.
T – Tremors
C – Cardiovascular side effects like arrhythmias, postural hypotension especially in those who have Ischemic heart disease.
A – Anticholinergic side effects like dry mouth, constipation, palpitation, urinary retention due to TCA’s have little activity to block muscarinic receptors.
S – Sedations and seizures
SSRI’S – Selective Serotonin Reuptake Inhibitors
S – Serotonin syndrome (a clinical triad of abnormalities due to excess level of serotonin– cognitive, autonomic, and somatic effects)
S – Stimulate CNS (Increase rate of breathing, aggression, irritability)
R – Reproductive dysfunction in male (decrease sexual desire or make you impotence for temporary)
I – Insomnia (unable to sleep)
Venlafaxine – increase the risk of QT prolongation (Tachycardia – means your heart rate may fall in between 100 to 300 beats per minute)
If you are dealing with depression for a long period you may have thoughts of killing/harm yourself.
In 2004, the FDA (Federal drug administration) issued a black-box warning for the nine antidepressant drugs – citalopram, paroxetine, fluoxetine, fluvoxamine, sertraline, venlafaxine, mirtazapine, bupropion, and nefazodone that significantly increased the risks of suicidality.
If you have previously had thought of killing yourself, you must consult your doctor before taking these antidepressants.
Are antidepressant drugs safe in pregnancy?
Generally, most antidepressants have a 60% risk of miscarriage in pregnancy.
Although, Mirtazapine is the safest antidepressant drug in pregnancy as per research.
Some scientific evidence suggests that all SSRIs are considered as the first-line antidepressants in pregnancy but they should be used when strictly indicated.
Still, you must consult your doctor if you are pregnant or planning to have a baby.
Which medicines should not be taken with antidepressant drugs?
Some drugs may cause some possible life-threatening effects if antidepressants given with other medicine or other antidepressants.
You should strictly avoid these combinations or you may consult your psychiatrists before taking the below combination together.
Increase plasma concentrations of TCA’s drugs – increase toxicity.
TCA’s and SSRI’s
Increase risk of CNS sedation
Antiarrhythmic drugs e.g. amiodarone, quinidine, flecainide
Increase the risk of ventricular arrhythmias.
TCA’s and SSRI’s
Neurotoxic symptoms and serotonin syndrome effects
TCA’s and SSRI’s
Increase the risk of seizures
TCA’s and SSRI’s
Increase the risk of bleeding
Cheese foods (containing tyramine)
Is Antidepressant drugs a life-long treatment?
Depression is curable. You do not need to take medicine for life long.
It depends on the type of depression and the severity of depression. It is not like other chronic diseases such as diabetes, hypertension, rheumatoid arthritis, etc. where you need to take medicines lifetime.
Antidepressants work with fewer side effects which can be easily manageable.
You need to monitor your health status regularly. You should not abruptly discontinue antidepressant medicine with yourself as it may give you withdrawal symptoms.
You should consult with your psychiatrist; they will taper your dose slowly.
Antidepressants are effective drugs with fewer side effects and possible drug interactions.
These drugs may give good results with counseling, yoga, and exercise.
But the problem with depression is that patients feel these things won’t work. They feel helpless or hopeless.
Sometimes patients do not take medicines properly that’s why it is difficult to manage depression.
If the patient follows proper drug therapy and counseling. It can be cured easily.
I hope I covered all the common rising queries. Share this post to spread knowledge.
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- Dien Ho. Antidepressants and the FDA’s Black-Box Warning. AMA journal of ethics, 2012. https://journalofethics.ama-assn.org/article/antidepressants-and-fdas-black-box-warning-determining-rational-public-policy-absence-sufficient/2012-06
- Venlafaxine: more dangerous than most “selective” serotonergic antidepressants. Prescrire Int 2016 Apr;25(170):96-9. https://pubmed.ncbi.nlm.nih.gov/27186622/
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- Drug interaction with antidepressants https://bpac.org.nz/BPJ/2007/March/interactions.aspx