Anti Depression Medications |SSRIs and SNRIs


Anti depression medications include the older tricyclic antidepressants (TCAs) , the monoamine oxidase (MAO) inhibitors, the newer selective serotonin reuptake inhibitors (SSRIs) and the serotonin norepinephrine reuptake inhibitors (SNRIs).

TCAs and MAO Inhibitors are seldom used today. They have been largely replaced with SSRIs and SNRIs due to their superior efficacy and better side effect profile.

Depression is a mental health disorder and many people benefit from the anti depression medications.There occurs a deficiency in the chemicals (neurotransmitters) such as serotonin and norepinephrine in the brain and these chemicals have important connection with our mood.

Anti depression medications directly or indirectly increase the amount of these neurotransmitters and potentiate their actions thereby improving the symptoms of depression.

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs (Selective serotonin reuptake inhibitors) are the drugs of choice for you if you are an adult suffering from depression. The undesirable effects of TCAs like hypotension ,dry mouth, sedation and cardiac rhythm abnormalities are not seen with SSRIs also they are safe in overdose, if happens by mistake.

How do they act?

SSRIs act by preventing the reabsorption of serotonin from the spaces between the brain cells ( synaptic cleft ) which is their "work place" .They also increase the synthesis and the release of the serotonin.

Serotonin is important for keeping good mood and better sleep.

Absorption and Response time?

SSRIs are well absorbed after oral administration and metabolized by the liver so the dose needs to be adjusted if you have liver dysfunction.

Do not expect an instant response when you start takings SSRIs. It takes at least two weeks to produce a significant response and it may take as long as eight weeks for the effect to occur.

Common Side Effects

The common side effects that you may encounter with SSRIs are nausea, vomiting, diarrhea, fatigue, sexual dysfunction, changes in weight and sleep disturbances.

Serotonin Syndrome can Take Your Life

Serotonin syndrome is a life threatening condition caused by interaction of SSRIs and SNRIs with the drugs like triptan (used for the treatment migraine) and MAO inhibitors and occurs because the level of body serotonin is markedly raised. It can also occur if Saint Johns wort is used simultaneously with other anti depression medications, so be careful!

The symptoms experienced in this syndrome are agitation, nausea, diarrhea, rapid heart rate, hallucinations, loss of coordination, fluctuation in blood pressure and vomiting.

Less Common Side Effects

The SSRIs may also cause minor bleeding complications like easy bruising, petechiae ,purpura,hematoma and epistaxis as they interfere with platelet aggregation. Risk for bleeding is more if you are also using NSAIDs. Anticoagulation therapy should also be done with care while using SSRIs.

Every SSRI is Different from the Other

Potency, receptor specificity ,pharmacokinetic properties, side effect profile, interaction with other drugs of different SSRIs are different. This makes a particular drug more appropriate for a particular patient.

Properties of Individual SSRIs

I have briefly discussed the properties of the following SSRIs :

  • Fluoxetine (Prozac)
  • Sertraline (Zoloft)
  • Paroxitine (Paxil)
  • Fluvoxamine
  • Citalopram
  • Escitalopram

FLUOXETINE (Prozac) - A Prototype SSRI

Fluoxetine is the prototype SSRI like all SSRIs it is well absorbed orally and is metabolized in liver; it is a potent inhibitor of hepatic enzyme CYP2D6 which is involved in the metabolism of many drugs including neuroleptics, antiarrhythmics, and beta adrenergic antagonists. So in case you are taking any such drug the dose needs to be reduced.

The usual effective dose is 20mg per day but if adequate response is absent the dose can be raised to 80mg in 10mg to 20 mg step.

Nausea, vomiting, insomnia and anxiety are the common side effects but do not panic, they mostly resolve in one or weeks but sexual dysfunction may persist throughout this anti depression medication treatment.

SERTRALINE (Zoloft)

Sertraline absorption is enhanced by food. Enzyme induction is minimal so does not commonly cause significant drug interactions.

Starting dose is 50mg daily; maintenance dose is 100mg but can be increased up to 200mg if required.

Side effects of this anti depression medication include nausea, diarrhea, insomnia, sexual dysfunction. Sexual function can be improved with buproin 75mg to 15mg per day. The side effects are relatively uncommon with Sertraline as compared to other SSRIs.

PAROXITINE (Paxil)

Paroxitine inhibits CYPD60 and thus interferes with the metabolism of other drugs .

Effective dose is 20 mg daily.

In addition to the sexual dysfunction and nausea, it may also cause sedation dry mouth and blurred vision. The enteric coated controlled release formulation commonly does not cause nausea as other anti depression medication may do.

It must be avoided during pregnancy as it may cause congenital malformations.

FLUVOXAMINE

Fluvoxamine is a potent inducer of p4501A2 involved in the metabolism of Clozapine and Theophylline. Amongst SSRIs drug interactions are most likely to occur with Fluvoxamine.

Staring dose is 50mg per day, therapeutic dose ranges from150 to 250mg.Side effects are the same as other SSRIs.

CITALOPRAM and ESCITALOPRAM

Citalopram is least likely to cause sexual dysfunction among SSRIs more over it also relives the symptoms of anxiety the interaction with other drug is also significantly less than other SSRIs.

The usual starting dose is 20mg daily; therapeutic dose ranges from 20 to 40mg.

ESCITALOPRAM it is an isomer of Citalopram and is more potent. Escitalopram has a low side effect profile and less likely to cause drug interaction than other SSRIs.

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs (Serotonin norepinephrine reuptake inhibitors) inhibit the reuptake of both serotonin and norepinephrine from the synaptic cleft. The SNRIs are the next option for the treatment of depression if you do not respond to SSRIs.

The two available anti depression medications in SNRIs are Venlafaxine and Duloxetine.

VENLAFAXINE

Venlafaxine is well absorbed after oral administration, metabolized in the liver to active metabolites and excreted in urine, mild inhibitors of CYP26D and so do not cause significant drug interactions except for with MAO inhibitors.

Both immediate and extended release formulations are available The usual starting dose is 37.5mg twice daily if you do not respond to this dose it can be increased to 375mg daily in 3 divided doses.

Common side effects like other anti depression medications are include nausea, dizziness, insomnia, sedation and constipation. There is also an increased risk of GI bleeding. Venlafaxine may raise the blood pressure, usually the increase is small but it may be significant in some patients so you should monitor your blood pressure while using it.

Drugs that inhibit CYP2D6 like SSRIs can increase the level of Venlafaxine, this drug interaction is important if you are switching from SSRIs to SNRIs and may cause temporary intolerance but as soon as the SSRIs are out of your system you would be better able to tolerate Venlafaxine.

Be careful with the dose because overdose may cause serious adverse effects like seizures, and even death and if you are a heart patient you need to be even more careful.

ESVENLAFAXINE is the main active metabolite of Venlafaxine. It is not metabolized by CYP2D6 so SSRIs have no effect on its metabolism. Recommended dose is 50 mg per day.

DULOXETINE

Duloxetine has shown efficacy in treatment of diabetic neuropathy in addition to treatment of depression. It is extensively metabolized in liver and if you are suffering from hepatic insufficiency, you should not use it, nor if you are an end stage renal patient.

Duloxetine can be used in a dose of 20 or 30 mg per day and the amount can be raised to a maximum of 60mg daily if required.

As with other anti depression medications nausea, dry mouth and constipation are the common side effects. Sexual dysfunction may occur but is less common as compare to SSRIs and other anti depression medication.


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