Antidepressants

What is the cause of depression?

Originally thought that low levels of serotonin was the cause

Now not so clear but likely reduction in serotonin receptors in hippocampus

Would help explain why SSRI takes so long to work

What is the first line treatment for depression

SSRIs

What are MAOIs?

monoamine oxidase inhibitors - very early antidepressants, rarely used anymore as have lots of drug interactions and side effects

When would you see someone still taking an MAOI

Older patients who have been on them for years as taking someone off an antidepressant can sometimes make things much worse and they will be used to them

What is the MOA of MAOIs?

Inhibit the activity of MAO enzymes

MAO breaks down norepinephrine/serotonin and dopamine

Inhibiting MAO increases level of all three transmitters

Give examples of MAOIs

Phenelzine

Selegiline

Tranylcypromine

What is seleginine used for today other than depression?

Parkinsons

What are the side effects of MAOIs

weakness

headache

dizziness

fatigue

weight gain

impotence

What drugs should MAOIs not be taken in combination with?

Should not be used in combination with SSRI/Tricyclic as well as some analgesics such as morphine/Tramadol

Why can you not take MAOIs with these drugs

As they will increase serotonin to potentially dangerous levels causing confusion, hypertension, tremor, coma and possibly death

How long is the washout period for MAOIs?

14 days

What foods can interact with MAOIs?

cheese

certain meats such as venison

alcohol

some green vegetables i.e. broad beans

Give an example of a reversible MAOI

Moclobeminde

MOA Moclobemide

Reported to act by reversible inhibition of MAO type A - Therefore called RIMA

What is the washout period for moclobemide?

Short acting so medications can be changed with only one week washout period.

MOA of tricyclic antidepressants (TCAs)

Act by inhibiting re-uptake of norepinephrine and serotonin by blocking the transporters responsible for re-uptake of these neurotransmitters.

Increasing concentration of neurotransmitters in the synapses and triggering further neurotransmission.

What are TCAs used to treat?

Depression

Anxiety

Chronic pain (i.e. fibromyalgia, reflex sympathetic dystrophy syndrome)

IBS

Neuralgia

OCD

Nocturnalenuresis

PTSD

Tricyclics should be used with caution in...

Cardiovascular disease due to risk of arrythmias

How do TCA's cause arrhythmias?

They can induce bradycardia followed by tachycardia

Why can TCAs be used to treat IBS?

Tricyclics have antimuscarinic activity that blocks activity of the muscarinic acetylcholine receptor and so reduce intestinal mobility. Reduce cramps and return guts to their normal movement pattern

Give examples of some other side effects of TCAs

reduce bronchial secretions

urinary retention

dry mouth

confusion

What age groups are TCAs not normally given to?

Elderly as can cause increased confusion so can increase their risk of falls, meaning increased risks of hip fracture, surgery and death

Give examples of common TCAs

Amitriptyline

Clomipramine

Imipramine

Lofepramine

Nortriptyline

What TCAs can be used to treat fibromyalgia

Amitriptyline

Nortriptyline

Give examples of a drug related to tricyclics

Trazodone

When would trazodone be used

Very low doses would be used in elderly patients with dementia that become agitated as it has a sedating effect

What are some concerns surrounding tricyclics

Tricyclics are very dangerous in overdose so beware of how much you prescribe for a patient and use with caution in patients at high risk of suicide

MOA of SSRIs

Believed to work by increasing levels of neurotransmitter serotonin by limiting its re- absorption and pure SSRI have only a weak affinity for norepinephrine and dopamine transmitters

Serotonin receptors are known as 5- hydroxytryptamine (5-HT)

They are, therefore, cleaner with generally fewer side effects and better tolerated by patients

What are SSRIs used to treat?

Depression

Anxiety

OCD

Panic disorder

PTSD

Eating disorders

Where are 5-HT receptors found?

5-HT receptors are found in the peripheral and central nervous systems mediating both excitatory and inhibitory neurotransmission

What neurotransmitter do 5-HT receptors modulate the release of?

GABA

Dopamine

Epinephrine

Norepinephrine

Acetylcholine

What can these neurotransmitters influence?

Aggression, anxiety, cognition, learning memory, mood and sleep

What are the sexual side effects of SSRIs?

Dysfunction and reduced libido

What are the cardiac side effects of SSRIs

Some, especially citalopram, to be used with caution as can cause QT interval prolongation therefore dose dependant with citalopram

What are the haematological side effects of SSRIs

Affects anticoagulants (i.e. warfarin and aspirin) and also increased risk of GI bleeds.

What are the suicidal side effects of SSRIs

Possible increased risk of suicide especially in children and adolescents

* May only be prescribed in under-18s by a psychiatrist

What is the risk of overdose with SSRIs

Safer than other antidepressants e.g. amitriptyline

How do SSRIs affect epilepsy

may reduce fit threshold

Give some other general side effects of SSRIs

Nausea

Rash

Muscle aches

Insomnia

Sweating

After how long should SSRI side effects settle down

After the first week

Give examples of SSRIs

Citalopram

Escitalopram

Paroxetine

Sertraline

Fluoxetine

(Order is from MOST to LEAST toxic)

Give examples of other antidepressants

Duloxetine

Mirtazapine

Venlafaxine

What class of antidepressant is Duloxetine?

SNRI (serotonin norepinephrine up-take inhibitor)

What is duloxetine used for?

Depression (moderate to severe)

Neuropathic pain (diabetes, fibromyalgia)

Stress urinary incontinence

What are the side effects of duloxetine

Nausea

Insomnia

Dizziness

What class of antidepressant is mirtazapine

A presynaptic alpha2-adrenoreceptor antagonist. Also a noradrenergic and specific serotonergic antidepressant NaSSA

What is mirtazapine used for?

Depression

Anxiety

PTSD

What are the side effects of mirtazapine

Low dose causes drowsiness so best taken at night Higher dose more stimulant effect

What class of antidepressant is venlafaxine

Serotonin-norepinephrine re-uptake inhibitor (SNRI)

What is venlafaxine used for?

Major Depressive Disorder

Anxiety

Panic

Social phobia

Metabolized in the body into desvenlafaxine (by cytochrome P206 isoenzyme in the liver)

Often used in treatment of resistant depression

Give examples of other drugs with antidepressant properties

Antipsychotics such as risperidone

Lithium used in bipolar/mania mood stabilization

Give examples of some adverse effects of lithium

Possible adverse affects on kidney and thyroid function. If a patient is on long term lithium, monthly blood tests must be done to check kidney and thyroid function

What can risperidone treat?

Used as both an anti-psychotic and anti-depressant in patients with psychosis

What other conditions can antidepressants be used to treat?

Pain i.e. nerve damage or abnormal nerve function (neuropathic) and some muscle pains (fibromyalgia and sciatica)

How do tricyclics treat pain?

Tricyclics work by blocking the re-uptake of Noradrenaline and Serotonin (5-HT) into the nerve endings and increasing their levels in the pain control pathways

How do antidepressants benefit pain?

Direct effect on the mechanisms of the pain, and not through any effect on mood and also through beneficial effects on sleep

What are some antidepressants commonly used to treat pain?

Amitriptyline

Nortriptyline

Duloxetine

Duloxetine is also licensed for...

diabetic neuropathy

Prolongation of the QT interval can lead to...

A life threatening arrhythmia known as torsades de pointes

Which antidepressant can prolong the QT interval

Citalopram

Use of more than one drug that prolongs the QT interval increases the risk of...

Torsades de pointes and ventricular arrhythmia

People who have more risk factors for QTc prolongation than the general population are particularly vulnerable to

Drug-induced LQTS

Who is more vulnerable to QTc prolongation

Major psychiatric disorders

Cardiovascular disease

The elderly

Women