Antidepressants Flashcards by Andy Ablett

How does the efficacy of different antidepressants differ?

Antidepressant efficacy is similar so selection is based on past history of a response, side effect profile and coexisting medical conditions.

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There is a delay typically of ____weeks after a therapeutic dose is achieved before symptoms improve.

2-4

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If no improvement is seen after a trial of adequate length (________) and adequate dose, either switch to another antidepressant or augment with another agent.

at least 2 months

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What is the prophylaxis; how long should a patient keep taking anti-depressants even if they feel better after a depressive episode?

First episode continue for 6mth to a year
Second episode continue for 2 years
Third episode disucuss life long

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Give 5 classifications of antidepressants

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

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Tricyclic antidepressants (TCA) are very effective but have a potentially unacceptable side effect profile i.e.???

antihistaminic, anticholinergic, antiadrenergic
Lethal in overdose (even a one week supply can be lethal!)
Can cause QT lengthening even at a therapeutic serum level

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Tertiary TCAs have tertiary ______ side chains

Amine

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Tertiary TCAs have tertiary amine side chains.

Side chains are prone to? Give examples

Cross react with other types of receptors which leads to more side effects

Examples:

Imipramine
amitriptyline
doxepin
clomipramine

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Secondary tricyclic antidepressants (TCAs) are of metabolites of which amines?

Tertiary amines

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How do secondary tricyclic antidepressants work?

primarily block noradrenaline

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What are the side-effects of secondary TCAs?

Give examples

Side chains are prone to cross react with other types of receptors which leads to more side effects

Desipramine
notrtriptyline

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Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

How do MAOIs work?

Bind irreversibly to monoamine oxidase thereby preventing inactivation of amines such as norepinephrine, dopamine and serotonin leading to increased synaptic levels.

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Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

MAOIs aree very effective for what type of depression?

Are very effective for resistant depression

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Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

MAOIs have what side effects?

Side effects include orthostatic hypotension
weight gain
dry mouth
sedation
sexual dysfunction
sleep disturbance

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Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

MAOIs can have a “cheese reaction”… what is it?

Hypertensive crisis can develop when MAOI’s are taken with tyramine-rich foods or sympathomimetics. *Cheese + Wine Reaction!!

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Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

Which foods and drinks must patients taking MAOIs stay away from?

Why?

Hypertensive crisis can develop when MAOI’s are taken with tyramine-rich foods or sympathomimetics.

*Cheese + Wine Reaction!!

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Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

What can happen if you take MAOIs with meds that increase serotonin or have a sympathomimetic action?

Serotonin syndrome

abdominal pain
diarrhea
sweats
tachycardia
HTN
myoclonus
irritability
delirium
Can lead to hyperpyrexia
cardiovascular shock and death

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Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

If MAOIs are taken with meds that increase serotonin or have a sympathomimetic action it can cause serotonin syndrome… what are the symptoms?

Serotonin syndrome

abdominal pain
diarrhea
sweats
tachycardia
HTN
myoclonus
irritability
delirium
Can lead to hyperpyrexia
cardiovascular shock and death

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Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

If MAOIs are taken with meds that increase serotonin or have a sympathomimetic action it can cause serotonin syndrome… How can you avoid this from happening?

To avoid need to wait 2 weeks before switching from an SSRI to an MAOI.

The exception of fluoxetine where need to wait 5 weeks because of long half-life.

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Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

How do selective serotonin reuptake inhibitors (SSRIs) work?

Block the presynaptic serotonin reuptake

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Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

What are SSRIs they used to treat?

Treat both anxiety and depressive sx

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Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

What are the most common side-effects of SSRIs?

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Most common side effects include

GI upset, sexual dysfunction (30%+!)
anxiety
restlessness
nervousness
insomnia
fatigue or sedation
dizziness

*Very little risk of cardiotoxicity in overdose

Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

What syndrome might patients develop if SSRIs are stopped too quickly?

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Can develop a discontinuation syndrome if drug stopped too quickly with

agitation
nausea
disequilibrium
dysphoria

Antidepressants used in psychiatry fall into the following categories;

Tricyclics (TCAs)
Monoamine Oxidase Inhibitors (MAOIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs)
Novel antidepressants

One draw back of using SSRIs is that some patients experience activation syndrome as they go onto it.

What is it caused by and what is it?

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Activation Syndrome: Cause increased serotonin. Can be distressing for patient.

Nausea
increased anxiety
panic
agitation.

Antidepressants used in psychiatry fall into the following categories; * Tricyclics (TCAs) * Monoamine Oxidase Inhibitors (MAOIs) * Selective Serotonin Reuptake Inhibitors (SSRIs) * Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs) * Novel antidepressants One draw back of using SSRIs is that some patients experience activation syndrome as they go onto it. Cause increased serotonin. Can be distressing for patient . How long does it last for?

Typically last 2 – 10 days Warn patients!

Antidepressants used in psychiatry fall into the following categories; * Tricyclics (TCAs) * Monoamine Oxidase Inhibitors (MAOIs) * Selective Serotonin Reuptake Inhibitors (SSRIs) * Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs) * Novel antidepressants If SSRIs are stopped too quickly it can cause discontinuation syndrome. What are the symptoms and what is the solution?

* agitation * nausea * disequilibrium * dysphoria More common with shorter half-life drugs so consider switching to fluoxetine (type of SSRI) .

* Short half life with no active metabolite means no build-up (which is good if hypomania develops) * Sedating properties (dose at night) offers good initial relief from anxiety and insomnia

* Sedating * wt gain * more anticholinergic effects * Likely to cause a discontinuation syndrome

* Very weak P450 interactions (only slight CYP2D6) * Short half life with lower build-up of metabolites * Less sedating when compared to paroxetine

* Max absorption requires a full stomach * Increased number of GI adverse drug reactions

Antidepressants used in psychiatry fall into the following categories; * Tricyclics (TCAs) * Monoamine Oxidase Inhibitors (MAOIs) * Selective Serotonin Reuptake Inhibitors (SSRIs) * Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs) * Novel antidepressants Fluoxetine (prozac) is a type of SSRI. What are the pros?

* Long half-life so decreased incidence of discontinuation syndromes. Good for pts with medication noncompliance issues * Initially activating so may provide increased energy * Secondary to long half life, can give one 20mg tab to taper someone off SSRI when trying to prevent SSRI Discontinuation Syndrome

Antidepressants used in psychiatry fall into the following categories; * Tricyclics (TCAs) * Monoamine Oxidase Inhibitors (MAOIs) * Selective Serotonin Reuptake Inhibitors (SSRIs) * Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs) * Novel antidepressants Fluoxetine (prozac) is a type of SSRI. What are the cons?

* Long half life and active metabolite may build up (e.g. not a good choice in patients with hepatic illness) * Significant P450 interactions so this may not be a good choice in pts already on a number of meds * Initial activation may increase anxiety and insomnia * More likely to induce mania than some of the other SSRIs

* Low inhibition of P450 enzymes so fewer drug-drug interactions * Intermediate ½ life

* Dose-dependent QT interval prolongation with doses of 10-30mg daily- due to this risk doses of \>40mg/day not recommended! * Can be sedating (has mild antagonism at H1 histamine receptor) * GI side effects (less than sertraline)

* Low overall inhibition of P450s enzymes so fewer drug-drug interactions * Intermediate 1/2 life * More effective than Citalopram in acute response and remission

* Dose-dependent QT interval prolongation with doses of 10-30mg daily * Nausea, headache

* Shortest ½ life * Found to possess some analgesic properties

* Shortest ½ life * GI distress, headaches, sedation, weakness * Strong inhibitor of CYP1A2 and CYP2C19

Inhibit both serotonin and noradrenergic reuptake like the TCAS but without the antihistamine, antiadrenergic or anticholinergic side effects

* Used for depression * anxiety * possibly neuropathic pain

* Minimal drug interactions and almost no P450 activity * Short half life and fast renal clearance avoids build-up (good for geriatric populations)

* Can cause a 10-15 mmHG dose dependent increase in diastolic BP. * May cause significant nausea, primarily with immediate-release (IR) tabs * Can cause a bad discontinuation syndrome, and taper recommended after 2 weeks of administration * Noted to cause QT prolongation * Sexual side effects in \>30%

* Some data to suggest efficacy for the physical symptoms of depression * Thus far less BP increase as compared to venlafaxine, however this may change in time

* CYP2D6 and CYP1A2 inhibitor * Cannot break capsule, as active ingredient not stable within the stomach * In pooled analysis had higher drop out rate

Antidepressants used in psychiatry fall into the following categories; * Tricyclics (TCAs) * Monoamine Oxidase Inhibitors (MAOIs) * Selective Serotonin Reuptake Inhibitors (SSRIs) * Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs) * Novel antidepressants Mirtazapine is a novel antidepressant. What are the pros?

* Different mechanism of action may provide a good augmentation strategy to SSRIs. Is a 5HT2 and 5HT3 receptor antagonist * Can be utilized as a hypnotic at lower doses secondary to antihistaminic effects

Antidepressants used in psychiatry fall into the following categories; * Tricyclics (TCAs) * Monoamine Oxidase Inhibitors (MAOIs) * Selective Serotonin Reuptake Inhibitors (SSRIs) * Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs) * Novel antidepressants Mirtazapine is a novel antidepressant. What are the cons?

* Increases serum cholesterol by 20% in 15% of patients and triglycerides in 6% of patients * Very sedating at lower doses. At doses 30mg and above it can become activating and require change of administration time to the morning. * Associated with weight gain (particularly at doses below 45mg

Antidepressants used in psychiatry fall into the following categories; * Tricyclics (TCAs) * Monoamine Oxidase Inhibitors (MAOIs) * Selective Serotonin Reuptake Inhibitors (SSRIs) * Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs) * Novel antidepressants Mirtazapine is a novel antidepressant. What are the cons?

Antidepressants used in psychiatry fall into the following categories; * Tricyclics (TCAs) * Monoamine Oxidase Inhibitors (MAOIs) * Selective Serotonin Reuptake Inhibitors (SSRIs) * Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs) * Novel antidepressants Buproprion is a novel antidepressant. What are the pros?

* Good for use as an augmenting agent * Mechanism of action likely reuptake inhibition of dopamine and norepinephrine * No weight gain, sexual side effects, sedation or cardiac interactions * Low induction of mania * Is a second line ADHD agent so consider if patient has a co-occurring diagnosis

Antidepressants used in psychiatry fall into the following categories; * Tricyclics (TCAs) * Monoamine Oxidase Inhibitors (MAOIs) * Selective Serotonin Reuptake Inhibitors (SSRIs) * Serotonin/Noradrenaline Reuptake Inhibitors (SNRIs) * Novel antidepressants Buproprion is a novel antidepressant. What are the cons?

* May increase seizure risk at high doses (450mg+) and should avoid in patients with Traumatic Brain Injury, bulimia and anorexia. * Does not treat anxiety unlike many other antidepressants and can actually cause anxiety, agitation and insomnia * Has abuse potential because can induce psychotic sx at high doses

**Case 1** * Susie has a nonpsychotic unipolar depression with no history of hypomania or mania. She has depressed mood, hyperphagia, psychomotor retardation and hypersomnolence. What agent would you like to use for her? * Establish dx: Major depressive disorder * Target symptoms: depression, hyperphagia, psychomotor retardation and hypersomnolence How should you treat her?

**For a** **treatment naive** **patient start with an SSRI.** Using the side effect profile as a guide select an SSRI that is less sedating. Good choices would be * Citalopram * Fluoxetine * Sertraline

* Less desirable choices include Paroxetine and Mirtazapine because of sedation and wt gain. * Not a duel reuptake inhibitors because she is treatment naïve. * Not a TCA because of side effects Instead, use an SSRI for naive patients; * Citalopram * Fluoxetine * Sertraline

**Case 2** ob is a 55 year old diabetic man with mild HTN and painful diabetic neuropathy who has had previous depressive episodes and one suicide attempt. He meets criteria currently for a major depressive episode with some anxiety. He has been treated with paroxetine, sertraline and buproprion. His depression was improved slightly with each of these meds but never remitted. What would you like to treat him with? * Establish dx: Major depressive disorder with anxious features * Target symptoms: depressive sx, anxiety and possibly his neuropathic pain

Assuming he received adequate trials previously would move on to a duel reuptake inhibitor as he had not achieved remission with two SSRIS or a novel agent. * Given his mild HTN would not choose Venlafaxine. * TCA’s can help with neuropathic pain and depression however not a good choice given the SE profile and lethality in overdose. **DRUG of Choice = Duloxetine** * Duloxetine is a good choice since it has an indication for neuropathic pain, depression and anxiety. Three birds with one stone!! * Keep in mind Duloxetine is a CYP2D6 and CPY1A2 inhibitor and has potential drug-drug interactions.

How should you treat a depressed patient with treatment resistance?

* Combination of antidepressants eg SSRI or SNRI (venlafaxine) with Mirtazepine * Adjunctive treatment with Lithium * Adjunctive treatment with atypical antipsychotic eg Quetipaine, Olanzapine or Aripiprazole * ECT!!

Antidepressants Flashcards

(54 cards)