QuestionSBA
QuestionChoice
The most common side effect of terazosin is dizziness, light-headedness, and orthostatic hypotension.
62275
c
Terazosin
QuestionChoice
The most common side effect of OTC fibre supplements is digestive discomfort, including bloating, gas, and diarrhoea. They are usually mild and can be relieved by drinking plenty of water.
62277
e
Over the counter fibre supplements
QuestionChoice
The most common side effect of amlodipine is swelling of the ankles and feet (peripheral oedema).
62274
b
Amlodipine
QuestionChoice
The most common side effect of alendronate is heartburn and difficulty swallowing. Rare but serious side effects include oesophageal irritation or ulcers, osteonecrosis of the jaw, and hypocalcaemia.
62276
d
Alendronate
QuestionChoice
Sertraline is a selective serotonin reuptake inhibitor used to treat depression and anxiety disorders. It is the most likely cause of his gastrointestinal symptoms, as nausea, vomiting, and diarrhoea are common side effects of SSRIs. Non-pharmacologic methods should be tried first in appropriate circumstances when treating the elderly. Behavioural therapy, relaxation techniques, and counselling should be tried first in a grief reaction.
62273
a
Sertraline
Concept
Chapter
# Summary

Antidepressants encompass a variety of classes of drugs which despite the name, are used to treat multiple conditions other than depression, such as anxiety, panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, and phobic states such as social anxiety disorder. Tricyclic antidepressants and monoamine oxidase inhibitors are older classes though are sometimes still used today, with selective serotonin reuptake inhibitors (SSRIs) becoming popular over the last decade due to their more favourable side effect profiles and lower risk of toxicity. Important considerations of these drugs include their side effects, monitoring, 


# Selective serotonin reuptake inhibitors (SSRIs)

## Mechanism of action

SSRIs selectively inhibit serotonin reuptake, increasing its availability and enhancing mood regulation.

## Indications

- SSRIs are first line for medical management of depression, generalised anxiety disorder (GAD), panic disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and phobic states such as social anxiety disorder. 

Cautions: 
- Should be omitted in mania
- Should be used with caution in children and adolescents
- Sertraline is best for patients with ischaemic heart disease
- Should be avoided in patients taking warfarin, due to increased risk of bleeding

## Side effects

SSRIs have a number of recognised side effects. These include:

- GI upset
- Anxiety and agitation
- QT interval prolongation (especially associated with citalopram)
- Sexual dysfunction
- Hyponatraemia
- Gastric Ulcer

## Monitoring

- In people aged 18-25 there is an increased risk of impulsivity and suicidal risk upon commencing antidepressant medication and so they should have a follow-up appointment arranged after one week to monitor progress. Initial reviews can otherwise be arranged 2-4 weeks after starting medication in patients >25.
- Continuation of antidepressants for at least six months post-remission is recommended to mitigate relapse risk. Tapering should be done gradually over a four-week period when discontinuing antidepressants.

## Serotonin syndrome

Serotonin syndrome, also known as serotonin toxicity, is a potentially life-threatening condition linked with increased serotoninergic activity in the central nervous system. It typically presents within the first few months of starting a Selective Serotonin Reuptake Inhibitor (SSRI) or due to drug interactions (SSRI + tramadol). The syndrome is characterised by a triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. It is a clinical diagnosis, and management strategies include discontinuation of the offending drug and supportive care. Please see separate section in Emergency Medicine section for more information.


# Serotonin and norepinephrine reuptake inhibitors (SNRIs)

## Mechanism of action

SNRIs work by increasing serotonin and norepinephrine levels, improving mood and anxiety.


## Indications

- SNRIs such as venlafaxine can also be used as first line pharmacological treatment of depression if SSRIs are not indicated or have been unsuccessful.
- Venlafaxine and duloxetine are also licensed for treatment of generalised anxiety disorder (GAD) and panic disorder.
- Contraindicated in those with a history of heart disease and high
blood pressure

## Side effects

Common side effects include:

* Nausea
* Insomnia
* Increased heart rate
* Agitation


# Noradrenergic and specific serotonergic antidepressant (NaSSA)


## Mechanism of action

NaSSAs such as mirtazepine also work by modulating norepinephrine and serotonin levels in the brain.

## Indications

- Mirtazepine is a second line choice of medication for management of depression, though may be preferred if in particular there are concerns over weight loss, as one of it's side effects is increased appetite. It may also be preferred if there are issues with getting to sleep as it is a light sedative and so it is usually taken in the evening.

## Side effects

* Sedation
* Increased appetite
* Weight gain
* Constipation/diarrhoea

# Tricyclic antidepressants (TCAs)

## Mechanism of action

Tricyclic and related antidepressants block the re-uptake of both serotonin and noradrenaline, and examples include amitriptyline, clomipramine and imipramine. They are also antimuscarinic (see contraindications and side effects below).

## Indications

They are another example of second line choices for treatment of depression, and are sometimes. used in the management of panic and other anxiety disorders.

Cautions:

- Contraindicated in those with previous heart disease
- Can exacerbate schizophrenia
- May exacerbate long QT syndrome
- Use with caution in pregnancy and breastfeeding
- May alter blood sugar in T1 and T2 diabetes mellitus
- May precipitate urinary retention, so avoid in men with enlarged prostates
- Uses the Cytochrome P450 metabolic pathway, so avoid in those on other CP450 medications or those with liver damage

## Side effects

Tricyclic anti-depressants are a second line medication for depression. They are strongly associated with anti-cholinergic activity. Consequently, the common side effects include:

- Urinary retention
- Drowsiness
- Blurred vision
- Constipation
- Dry mouth

## Toxicity

Key signs and symptoms include drowsiness, confusion, arrhythmias, seizures, vomiting, headache, flushing, and dilated pupils. Essential investigations include blood tests (FBC, UE, CRP, LFTs), Venous Blood Gas, and an ECG to check for QT interval prolongation. The management primarily involves supportive care based on patient symptoms, with considerations for activated charcoal within 2-4 hours of the overdose and intensive care review in severe cases.

# Monoamine oxidase inhibitors (MAO-Is)


## Mechanism of action

Monoamine oxidase (MAO) normally metabolises serotonin and noradrenaline in the presynaptic cell. MAO inhibitors inhibit monoamine oxidase which leads to an elevation in brain levels of catecholamines and serotonin. It has a similar structure to amphetamine so this also affects the uptake and release of dopamine, noradrenaline, and serotonin.

Examples include moclobemide (MAO-B inhibitor), phenelzine (MAO-A inhibitor).

## Indications

They were historically used to treat depression but are used less frequently now.

Cautions:

* Cerebrovascular disease
* Manic phase of bipolar disorder
* Phaeochromocytoma
* Severe cardiovascular disease

## Side effects

* Hypertensive reactions ('cheese reaction') with tyramine-containing foods (so patients need to avoid pickled herring, Bovril, Oxo, Marmite, cheese, salami).
* Should also avoid broad bean pods as these contain dopa.

# References

[Click here to see the BNF summary for antidepressants](https://bnf.nice.org.uk/treatment-summary/antidepressant-drugs.html)
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Antidepressants
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Psychiatry
12516
A 54-year-old man with a history of hypertension, osteoporosis, benign prostatic hyperplasia, and constipation comes to the clinic ten months after the death of his spouse. He reports decreased appetite and difficulty sleeping and performing daily activities. He is currently taking amlodipine, terazosin, alendronate, and over-the-counter fibre supplements and recently started sertraline for depression. He is now complaining of diarrhoea, nausea and vomiting.

Which of the following drugs would have led to his complaints?
a