Antidepressants Flashcards
What are the causes 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
- Many studies show people with depression having what is assumed to be normal levels of serotonin
What are Mono Amine Oxadase Inhibitors (MAOI) ?
These are older anti-depressants which agents really used a whole lot anymore
Mono Amine Oxadase Inhibitors (MAOI);
- Inhibit the activity of MAO enzymes
- They were the first class of antidepressants developed
- MAO breaks down norepinephrine / serotonin and dopamine
- Inhibiting MAO increases level of all three transmitters
MAOI
- Phenelzine
- Selegiline - also used in Parkinson’s
- Tranylcypromine
Side effects;
- Weakness dizziness
- Headache fatigue
- Weight gain impotence
What are interactions MAOI may have?
They should not be used with SSRI / Tricyclic as well as some analgesics such as morphine / Tramadol as they will increase serotonin to potentially dangerous levels causing confusion, hypertension, tremor, coma and possibly death
Give 14 days washout after stopping MAOI before starting other antidepressants
Foods high in tyramine may also cause a hypertensive crisis;
- Cheese
- Certain meats such as venison
- Alcohol
- Some green vegetables (e.g broad beans)
How can we reverse MAOI?
Moclobeminde;
Report to act by reversible inhibition of MAO type A
- Therefore called RIMA
- Tyramine has less of an effect
- Short acting so medications can be changed with only one week washout period
What are Tricyclic Antidepressants ?
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 the uses for Tricyclic Antidepressants ?
Uses;
- Depression
- Anxiety
- Chronic pain (e.g fibromyalgia, reflex sympathetic dystrophy syndrome)
- IBS
- Neuralgia
- OCD
- Nocturnal enuresis
- PTSD
What are some of the side effects of Tricyclic Antidepressants ?
Should be used in caution with cardiovascular disease due to risk of arrythmias
Have antimuscarinic avidity that blocks activity of the muscarinic acetylcholine receptor and so reduce intestinal mobility
They can induce bradycardia followed by tachycardia, reduce bronchial secretions, urinary retention, dry mouth and confusion
What are some common Tricyclic Antidepressants ?
Common Tricyclics;
- Amitriptyline
- Clomipramine
(These 2 are most common for fibromyalgia and chronic pain - back problems, slipped disc)
- Imipramine
- Lofepramine
- Nortriptylin
Name a drug related to the Tricyclics?
Trazodone - More sedating
Concerns - tricyclics are very dangerous in overdose so b aware of how much you prescribe for a patient and see with caution in patients at high risk of suicide.
Dispense lower quantities to these suicidal patients more frequently as a preventative procedure - check mental health and overdose risk
What are Selective Serotonin Re-uptake Inhibitors (SSRI)?
Selective Serotonin Re-uptake Inhibitors (SSRI) are 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
They are the most widely prescribed antidepressants
What are uses for SSRI anti-depressants ?
Uses;
- Depression
- Anxiety
- OCD
- Panic disorder
- PTSD
- Eating disorder
- Menopausal symptoms - more women prefer due to risk with taking hormone replacement therapy and cancer
How do 5-HT receptors in SSRI’s work chemically?
5-HT receptors are found in the peripheral and central nervous systems mediating both excitatory and inhibitory neurotransmission
These receptors modulate the release of many neurotransmitters;
- GABA
- Dopamine
- Epinephrine
- Norepinephrine
- Acetylcholine
They influence aggression, anxiety, condition, learning memory, mood and sleep
What are the SSRI side effects?
- Sexual dysfunction and reduced libido
- Cardiac, some, especially citalopram, to be used with caution as can cause QT interval prolongation therefore dose dependant with citalopram
- Bleeding, affects anticoagulants (i.e warfarin and aspirin) and also increased risk of GI bleeds
- Suicide, possible increased risk of suicide especially in children and adolescents (can only prescribe under-18’s by psychiatrist)
- Overdose: safer than other antidepressants
- Epilepsy, may reduce fit threshold
Others;
- Nausea
- Rash
- Muscle aches
- Insomnia
- Sweating (Can confuse with worry of cancer from having night time sweats)
What are the most toxic to least toxic SSRI’s?
Citalopram (QT interval)
Escitalopram
Paroxetine
Sertraline
Fluoxetine
When stop patients get quite agitated
What are some other antidepressants that can be offered?
Duloxetine: SNRI (Serotonin norepinephrine up-take inhibitor)
Uses - depression, neuropathic pain (diabetes, fibromyalgia), stress urinary incontinence
Side effects - Nausea, insomnia, dizziness
Mirtazapine: A presynaptic alpha2-adrenoreceptor antagonist. Also a noradrenergic and specific serotonergic antidepressant - NaSSA
Uses - depression, anxiety, PTSD
Side effects - Low dose causes drowsiness so best taken at night. Higher dose more stimulant effect so take in morning
Venlafaxine: SNRI (Serotonin norepinephrine up-take inhibitor)
Uses - major depressive disorder, anxiety, panic, social phobia, metabolised in the body into desvenlafaxine (by cytochrome P206 isoenzyme in the liver). Often used in treatment of resistant depression.