Is There Still a Role for First-generation Antidepressants?

Antique medicine cabinet

Since the introduction of fluoxetine, the first “second generation antidepressant”, in 1988, drug brand names such as Prozac, Lexapro and Zoloft have become household words. But what about the “first-generation antidepressants”? Even to many of the millions of Americans who struggle with depression, medications such as Elavil, Pamelor, and Tofranil, some of the earliest depression medications, may sound unfamiliar.

First generation antidepressant drug treatment, for the most part, involved two major classes of drugs:    tricyclic antidepressants and monoamine oxidase inhibitors.  Tricyclic depression medication works by increasing levels of certain neurotransmitters, or chemicals, in the brain.  Unlike the newer depression medications, most of which selectively increase serotonin, the tricyclics are non-selective and increase serotonin, norepinephrine and, to a lesser extent, dopamine.  They also interfere with the action of other chemicals, such as histamine.  Although they are effective in elevating mood and decreasing anxiety, because they have so many and varied actions, they have considerably more side-effects than the newer agents.  The most common undesirable effects are drowsiness, dry mouth, dizziness, blurred vision, increased appetite, weight gain, palpitations, and sexual dysfunction. Tricyclic overdosage is extremely toxic, and is one of the leading causes of death due to drug overdose in the United States. For this reason, this class of medication is relatively contraindicated in severely depressed patients at risk for suicide.

Because of the relatively high incidence of side-effects with tricyclic anti-depressants, they are rarely used today as first line therapy for depression.  On the other hand, due to their non-selectivity and multiple actions, they are useful for a number of other indications and, fortunately, are often effective in smaller doses than would be required for depression treatment. Thus, they are better tolerated and cause fewer undesirable symptoms. Protriptyline (Vivactil) and desipramine (Norpramine) are used to treat Attention Deficit Hyperactivity Disorder (ADHD). Clomipramine (Anafranil) can relive the symptoms of obsessive-compulsive disorder (OCD) and narcolepsy. Imipramine (Tofranil) has been shown to be effective in the treatment of bed-wetting.

Monoamine oxidase (MAO) inhibitors, such as phenelzine (Nardil) and tranylcypromine (Parnate) also increase neurotransmitter levels in the brain.  They do this by inhibiting the enzyme, monoamime oxidase, that breaks down the neurotransmitters. Like the tricyclics, they are effective in relieving depression, but their use today is limited by their side-effects. One of their most serious adverse effects involves a reaction that takes place when a person taking an MAO inhibitor ingests a food containing tyramine.  The combination is extremely toxic and may result in a marked rise in blood pressure, headache, nausea, vomiting, confusion, seizures, stroke, coma or death. Strict adherence to a restricted diet is essential and tyramine-rich foods, such as aged cheese, smoked or processed meats, fish and soy products, red wine, fava beans, ripe figs, and foods containing monosodium glutamate MSG), must be avoided.  MAO inhibitors can also have dangerous interactions with alcohol, local anesthetics, cold and allergy medication, and a number of prescription drugs.  They are still prescribed occasionally, and can provide relief to some patients who have not responded to other therapies.  With careful monitoring and strict compliance to dietary restrictions, they can be used safely and successfully.

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  • <a href=””> Zoloft </a> is dangerous and I don`t understand why people still buying it?

  • Parnate saved my life!
    I’m a mental health advocate, Huffington Post blogger, and my book “Birth of a New Brain – Healing from Postpartum Bipolar Disorder” will be out in 2017. I’ve been anti-med. Been there, done that big-time, and I gave it my best, more researched, shot to try to live without medication. It didn’t work for me. Everyone has a right to make her own health treatment decisions, and my girls are relieved their mom is alive and happy because of tranylcypromine, or Parnate.

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