Why does anti-X medicine makes problems worse for some people?

[Diamonds02]

I’m talking about pills such as anti-depressants or anti-emetics.

Why does anti-depressants make some people more depressed? I knew a few friends who were only mildly to moderately depressed and became suicidal after taking pills like prozac.

My mother throws up everytime she takes Zofran, which I heard is supposed to be one of the best anti-nause pills out there.

What is going on in these cases?

[Exapno_Mapcase]

It’s called a paradoxical effect (or reaction). Why it happens isn’t completely clear.

Paradoxical Reactions to Benzodiazepines: Literature Review and Treatment Options.
Carissa E. Mancuso, Pharm.D.; Maria G. Tanzi, Pharm.D.; Michael Gabay, Pharm.D.

Abstract and Introduction
Abstract
Benzodiazepines frequently are administered to patients to induce sedation. Paradoxical reactions to benzodiazepines, characterized by increased talkativeness, emotional release, excitement, and excessive movement, are relatively uncommon and occur in less than 1% of patients. The exact mechanism of paradoxical reactions remains unclear. Most cases are idiosyncratic; however, some evidence suggests that these reactions may occur secondary to a genetic link, history of alcohol abuse, or psychological disturbances. This review evaluates the numerous cases of paradoxical reactions to benzodiazepines in adult and pediatric patients that have been reported in the biomedical literature. It also explores the advantages and disadvantages of the various available treatment options.

Introduction
Benzodiazepines are used primarily in the treatment of generalized anxiety and panic disorders, as sedative hypnotics, muscle relaxants, and anticonvulsants. These agents exert their pharmacologic action by binding to benzodiazepine-γ-aminobutyric acid (GABA)-type A-chloride receptors in the central nervous system.[1] This action results in increased inhibitory action of GABA, producing a state of relaxation and inducing anterograde amnesia.

Benzodiazepines commonly are given alone or in combination with anesthetics to induce sedation. Unfortunately, some patients experience paradoxical reactions to these agents.[1] These reactions are characterized by increased talkativeness, emotional release, excitement, excessive movement, and even hostility and rage. The pathophysiologic mechanisms underlying these reactions are unclear; however, several predisposing risk factors have been identified. These include young and advanced age, genetic predisposition, alcoholism, and psychiatric and/or personality disorders. Children and elderly patients may be more predisposed than other patients to paradoxical reactions with benzodiazepines. It has been theorized that these subgroups of patients have alterations in the pharmacodynamic response to benzodiazepines; however, the exact differences have not been specifically characterized in the literature.[2] Some patients may have a genetic variability in the benzodiazepine-GABA-chloride receptor that results in an abnormal pharmacodynamic response.[3] Multiple allelic forms of genetically determined benzodiazepine receptors exist, resulting in differing affinity for benzodiazepines among patients.

Patients who are alcoholic may be at increased risk of adverse reactions from benzodiazepines due to an alteration of the neuroregulatory mechanisms of the brain.[4] Alcoholics are believed to have decreased synthesis and functioning of GABA, resulting in less inhibitory action of the neurotransmitter. Finally, patients with psychiatric and/or personality disorders have an increased risk of paradoxical reactions to benzodiazepines.[5-7] In this group of patients, the highest risk is experienced by those with psychiatric histories of anger and aggressive behavior. The exact mechanism of paradoxical reaction development in these patients is unclear.[4]

[Keeve]

@Diamonds02

Why does anti-depressants make some people more depressed? I knew a few friends who were only mildly to moderately depressed and became suicidal after taking pills like prozac.

I might understand it if an anti-depressant would make some people more depressed. But that’s not what they’re warning us about. They’re warning us that it makes some people suicidal. I wonder why the increased depression is so specifically directed.

[Zsofia]

I read an article once that suggested that some people who become suicidal on antidepressants are actually feeling better - they were suicidal before but too depressed to act on it.

[KneadToKnow]

@Zsofia

I read an article once that suggested that some people who become suicidal on antidepressants are actually feeling better - they were suicidal before but too depressed to act on it.

OMG, that is exactly the impression I have always had of that effect. “Jeez, before I started taking this stuff, I wanted to die but couldn’t even muster up the wherewithal to do anything about it. Today I feel like I can do … well, not anything, but this one thing!”

[Squink]

@Exapno_Mapcase

Why it happens isn’t completely clear.

In some cases, the unwanted effects are related to individual differences in the rate at which drugs are metabolized. Variation in the activity of cytochrome p450 2d6 is notorious for causing unwanted reactions to some psych meds. While a dose of 100 mg per day might be appropriate for a normal metabolizer, it may lead to toxic plasma levels in a slow metabolizer, or subclinical levels in a rapid metabolizer.

[Wendell_Wagner]

According to A Beautiful Mind by Sylvia Nasar, the schizophenics who commit suicide are “people who got well enough between acute episodes to appreciate the awfulness of what lay ahead of them and succumbed to despair.” In other words, schizophrenics at their worst periods didn’t tend to commit suicide as much, because they didn’t know how bad things were. It was during periods of remission that they realized how hopeless their lives were that they more often committed suicide.