Lecture 6.2 Flashcards
(27 cards)
What is monoamine oxidase?
Monoamine oxidase is an enzyme that breaks down biogenic and sympathomimetic amines.
What is downregulation?
Downregulation is reduced cell sensitivity to the signalling molecule.
What do the abbreviations NNTB and NNTH stand for?
NNTB stands for number needed to treat for an additional beneficial outcome. NNTH stands for number needed to treat for an additional harmful outcome.
In the 1960s, what were the first-line treatments for MDD and GAD?
In the 1960s, first-line treatments for MDD were antidepressants, and first-line treatments for GAD were anxiolytics (even in the 1990s).
By the 21st century, what became the first-line treatment for both depression and anxiety?
By the 21st century, antidepressants became the first-line treatment for both depression and anxiety.
Describe the mechanism of action of Monoamine Oxidase Inhibitors.
Monoamine oxidase inhibitors inhibit the breakdown of neurotransmitters by monoamine oxidase. Monoamine oxidase is an enzyme that breaks down biogenic and sympathomimetic amines. MAO-A and MAO-B isoenzymes are present in the presynaptic terminal. MAOIs increase the amount of neurotransmitters available in the synapses for neural function.
What is the difference between MAOI-A and MAOI-B drugs?
MAOI-A drugs inhibit MAOs that target norepinephrine, dopamine, and serotonin. MAOI-B drugs inhibit MAOs that primarily target dopamine.
What does Davis et al. (2014) state about the efficacy of MAOIs compared to placebo in treating social anxiety?
Davis et al. (2014) state that MAOIs are more effective than placebo at reducing social anxiety.
According to Davis et al. (2014), which MAOIs were most effective against placebo?
According to Davis et al. (2014), phenelzine and moclobemide were the most effective MAOIs versus placebo.
Describe the therapeutic action of Tricyclic Antidepressants.
The therapeutic action of Tricyclic Antidepressants is to inhibit norepinephrine reuptake transporters, serotonin reuptake transporters, and to act as a negative allosteric modulator. TCAs bind to the allosteric site close to the neurotransmitter transporter, so the neurotransmitter can’t bind anymore. Norepinephrine and serotonin can’t be reabsorbed by the presynaptic neuron, resulting in more available in the synapse for potential binding.
What are the side effects of Tricyclic Antidepressants, and which receptors are involved?
Side effects of Tricyclic Antidepressants include dizziness due to adrenergic antagonism, memory impairments due to muscarinic antagonism, drowsiness due to histaminergic antagonism, and arrhythmias and cardiac arrest, as well as seizures, due to sodium channel blockages in the heart and brain.
What does Rickels et al. (1993) state about the efficacy of Tricyclic Antidepressants in reducing GAD symptoms compared to placebo?
Rickels et al. (1993) states that Tricyclic Antidepressants are more effective than placebo at reducing GAD symptoms.
According to Rickels et al. (1993), what were the improvement rates for patients treated with imipramine, diazepam, and placebo?
According to Rickels et al. (1993), among completers, 73% of patients treated with imipramine showed moderate to marked improvement, 66% of patients treated with diazepam showed moderate to marked improvement, and 47% of patients treated with placebo showed moderate to marked improvement.
Describe the mechanism of action of Selective Serotonin Reuptake Inhibitors.
Selective Serotonin Reuptake Inhibitors’ mechanism of action is selective and potent inhibition of serotonin reuptake, making them indirect agonists. The drug blocks the serotonin transport pump (SERT), so serotonin can’t be reabsorbed by the presynaptic neuron. This results in more serotonin in the synapse for potential binding by post-synaptic receptors for neural functioning. A flow-on effect of agonism is that pre-synaptic 5HT-1a autoreceptors habituate to excess serotonin and downregulate. The autoreceptor ‘brake’ gets weaker over time, meaning autoreceptors can’t inhibit serotonin release. The neuron becomes disinhibited, and serotonin ‘pours’ out of the cell to mediate SSRI effects.
How does Kopcalic et al. (2025) explain the efficacy of escitalopram in reducing GAD symptoms compared to placebo?
Kopcalic et al. (2025) explains that escitalopram is more effective than placebo at reducing GAD symptoms, resulting in a 50% reduction in scores.
Describe the mechanism of action of Serotonin Norepinephrine Reuptake Inhibitors.
Serotonin Norepinephrine Reuptake Inhibitors’ mechanism of action is the selective inhibition of serotonin and norepinephrine reuptake at their respective transporters, making them indirect agonists. The drug blocks serotonin and norepinephrine transport pumps (SERT, NET), so serotonin and norepinephrine can’t be reabsorbed by the presynaptic neuron. This results in more serotonin and norepinephrine in the synapse for neural functioning. They also have downregulation effects, as with SSRIs.
What do Kopcalic et al. (2025) and Kopcalic et al. (2025) state about the efficacy of duloxetine and venlafaxine, respectively, in reducing GAD symptoms compared to placebo?
Kopcalic et al. (2025) states that duloxetine is more effective than placebo at reducing GAD symptoms, resulting in a 50% reduction in scores. Kopcalic et al. (2025) states that venlafaxine is more effective than placebo at reducing GAD symptoms, resulting in a 50% reduction in scores.
What did the meta-analysis of 37 studies with 12,226 participants (Kopcalic et al., 2025) find when comparing SSRIs and SNRIs?
The meta-analysis of 37 studies with 12,226 participants (Kopcalic et al., 2025) found that, compared to placebo, both SSRIs and SNRIs are collectively more effective at reducing GAD symptoms and are equally as accepted, but are less tolerated due to side effects. There was no difference between SSRIs and SNRIs, but the relative risk for SSRIs was 1.51, and for SNRIs, it was 1.35.
What did the meta-analysis of 89 studies with 25,441 participants (Slee et al., 2019) find about the efficacy and acceptability of duloxetine, venlafaxine, escitalopram, sertraline, fluoxetine, paroxetine, and benzos?
The meta-analysis of 89 studies with 25,441 participants (Slee et al., 2019) found that duloxetine, venlafaxine, and escitalopram are efficacious with good acceptability. Sertraline and fluoxetine are the same, but limited by small samples. Paroxetine and benzos are effective but poorly tolerated.
What did the meta-analysis of 56 studies with 12,655 participants (Gomez et al., 2018) find when comparing SSRIs and SNRIs to benzodiazepines in treating GAD symptoms?
The meta-analysis of 56 studies with 12,655 participants (Gomez et al., 2018) found that, compared to placebo, both drug classes collectively are more effective at reducing GAD symptoms. However, SSRIs and SNRIs had significantly lower effect sizes compared to benzodiazepines, and this effect was unrelated to treatment length.
According to the meta-analysis and Bayesian probabilistic analysis of 27 studies (Baldwin et al., 2011), which drug had the greatest probability of being most effective at reducing symptoms and achieving remission, and which had the greatest probability of withdrawal due to AEs?
According to the meta-analysis and Bayesian probabilistic analysis of 27 studies (Baldwin et al., 2011), all drugs were more effective than placebo in reducing GAD symptoms. Fluoxetine had the greatest probability of being most effective at reducing symptoms and achieving remission. Sertraline had the greatest probability of withdrawal due to adverse events.
What did the meta-analysis of 24 studies (Beyer et al., 2011) suggest about the effectiveness of benzodiazepines versus antidepressants in treating different types of GAD symptoms?
The meta-analysis of 24 studies (Beyer et al., 2011) suggested that benzodiazepines are more effective than antidepressants at reducing somatic symptoms of GAD. There was a trend towards reducing psychic symptoms of GAD, but the effect did not reach statistical significance (p = .070).
According to Kopcalic et al. (2025), what is the NNTB for antidepressant efficacy and dropouts, and what is the NNTH for antidepressant dropouts due to AEs?
According to Kopcalic et al. (2025), the NNTB for antidepressant efficacy is 7, meaning 7 people need to be treated with an antidepressant for GAD for one more person to experience a response to treatment. The NNTB for antidepressant dropouts is 27, meaning treating 27 people with an antidepressant would result in one less person dropping out due to a lack of efficacy. The NNTH for antidepressant dropouts due to adverse events is 17, meaning treating 17 people would result in one more person dropping out due to an adverse effect.
Why are 2nd generation drugs preferred?
Second-generation drugs are preferred because they are more tolerable, rather than having better benefits, and they also have a reduced risk of dependence.
