Generalised Anxiety Disorder (GAD)

Question 1

Antidepressents

SSRI, Venlafaxine and mirtazapine

Answer 1

1. As an option for treatment of major depression where first-line SSRIs are ineffective or not tolerated
2. GAD (Venlafaxine)

Question 2

Venlafaxine and Mirtazepine

MOA

Answer 2

• Venlafaxine is a serotonin and noradrenaline reuptake inhibitor (SNRI), interfering with uptake of these neurotransmitters from the synaptic cleft.
• Mirtazapine is an antagonist of inhibitory pre-synaptic α2-adrenoceptors. Both drugs increase availability of monoamines for neurotransmission, which appears to be the mechanism whereby they improve mood and physical symptoms in moderate-to-severe (but not mild) depression.
• Venlafaxine is a weaker antagonist of muscarinic and histamine (H1) receptors than tricyclic antidepressants, whereas mirtazapine is a potent antagonist of histamine (H1) but not muscarinic receptors.
• They therefore have fewer antimuscarinic side effects than tricyclic antidepressants, although mirtazapine commonly causes sedation.

Question 3

Venlafaxine and mirtazapine

Adverse effects

Answer 3

• Common adverse effects of both drugs include GI-upset (e.g. dry mouth, nausea, change in weight and diarrhoea)
• Central nervous system effects (e.g. headache, abnormal dreams, insomnia, confusion and convulsions)
• Less common but serious adverse effects include hyponatraemia and serotonin syndrome
• Suicidal thoughts and behaviour may increase
• Venlafaxine increases QT interval and can increase the risk of ventricular arrhythmias
• Sudden drug withdrawal can cause GI upset, flu-like symptoms, sleep disturbances

Question 4

Venlafaxine and mirtazapine

Warnings

Answer 4

• As with many centrally acting medications, the elderly are at particular risk of adverse effects
• A dose reduction should be considered in people with hepatic or renal impairment
• Venlafaxine should be used with caution in paitents with CVD associated with an increased risk of arrhythmias

Question 5

Venlafaxine and mirtazapine

Important interacitons

Answer 5

• The combination of these drugs from other anti-depressant classes can increase the risk of adverse effects (including serotonin syndrome)

Question 6

Venlafaxine and mirtazapine

Communication

Answer 6

• Advise patients that treatment should improve symptoms over a few weeks, particularly sleep and appetite
• Discuss referring them for psychological therapy, which may offer greater long-term benefits than drug treatment
• Explaing that they should carry on with treatment for at least 6 months after they feel better to stop the depression from coming back
• Warn them not to suddenly stop = withdrawl. Gradual withdrawal must occur over 4 weeks
• Counsel patients on signs of blood disorders

Question 7

Gabapentin and pregabalin

Answer 7

1. Both drugs are used for focal epilepsies (with or without secondary generalisation), usually as an add-on treatment when other anti-epileptic drugs e.g. CBZ provide inadequate control
2. Both are used for neuropathic pain, pregabalin is particularly recommended as a 2nd line option for diabetic neuropathy
3. Gabapentin is used for migraine prophylaxis
4. Pregabalin is used for GAD

Question 8

Pregabalin and gabapentin

MOA

Answer 8

• From a structural point of view, gabapentin is closely related to GABA, the major inhibitory neurotransmitter in the brain
• However, its MOA although not completely understood, appears largely unrelated to GABA
• It binds with voltage-sensitive calcium channels (Ca2+), where it presumably prevents inflow of Ca2+ and in doing so, inhibits neurotransmitter release
• This interferes with synaptic transmission and reduces neuronal excitability
• Pregabalin is a structural analogue of gabapentin that probably has a similar MOA

Question 9

Gabapentin and pregabalin

Adverse effects

Answer 9

• Gabapentin and pregabalin are generally better tolerated than other anti-epileptics drugs
• Their main side effects are drowsiness, dizziness and ataxia, which usually imprvoe over the first few weeks of treatment

Question 10

Gabapentin and pregabalin

Warnings

Answer 10

• Both drugs depend on the kidneys for their elimination, so their doses should be reduced in renal impairment

Question 11

Gabapentin and pregabalin

Important interactions

Answer 11

• The sedative effects of gabapentin and pregabalin may be enhanced when combined with other sedating drugs (e.g. BZs)
• Other than this, gabapentin and pregabalin are notable in having relatively few drug interactions- in stark contrast to most other anti-epileptic drugs
• This makes them particularly useful where combination regimens are considered necessary

Question 12

Gabapentin and pregabalin

Communication

Answer 12

• Explain that you are offering a medicine which you anticipate will reduce the severity of their symptoms (e.g. frequency of their fits)
• Explain that the medicine commonly causes some drowsiness and dizziness
• For this reason, you will prescribe a low dose initially, the increase this gradually (make surethey are clear on the dosing instructions)
• Explain that these side effects should improve over the first few weeks
• They should avoid driving or operating machines until they are confident that the symptoms have settled

Question 13

Gabapentin and pregabalin

Monitoring

Answer 13

• The best guide to clinical effectiveness is to enquire about symptoms (e.g. seizure frequency) and side effect
• There is no need to monitor serum/plasma concentrations of gabapentin or pregabalin