Pharmacological treatment of depression
Two recent Welsh Medicines Resource Centre bulletins give a useful overview of issues to consider in the pharmacological management of depression. The reader is directed to these bulletins for a comprehensive review of the subject.
Summary points taken from these bulletins are given below.
Who to treat
Antidepressant drugs are effective for treating moderate to severe depression. Ideally patients should be treated with psychological therapy in addition to drug therapy. Antidepressant therapy can also be effective for chronic low grade depression of at least two years duration.
Drug treatment of children and adolescents should be reserved for specialists. Only Fluoxetine has been shown in clinical trials to be effective in treating depressive illness in children and adolescents and, if used, patients should be monitored carefully for self harm and suicidal thoughts.
Classes of drugs available
The major classes of antidepressants are tricyclic and related antidepressants (TCAs), serotonin re-uptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs). A number of drugs cannot be included easily within this classification. MAOIs have dangerous interactions with some foods and drugs and should only be used by specialists.
St John's wort is available to the public as a herbal remedy for depression. However, it should not be prescribed because it can induce drug metabolising enzymes resulting in a number of important interactions with other drugs. In addition, the amount of active ingredient differs between different preparations.
Choice of treatment
There are no significant differences in efficacy between the different classes of drugs available to treat depression in adults. Choice of treatment is based on an assessment of co-morbidities, potential side effects and safety in overdose balanced against expected benefit. The strongest evidence for the efficacy of antidepressant therapy is for the treatment of depression of at least moderate severity.
NICE recommends Selective Serotonin Reuptake Inhibitors (SSRIs) as first choice as these have less side effects and are less toxic in overdose. In the absence of previous treatment a generic SSRI should usually be first line. There is no evidence of a clinically meaningful difference in efficacy between the different SSRIs, but side effect profiles do differ:
• Paroxetine has been associated with more weight gain and a higher incidence of sexual dysfunction. It is associated with more discontinuation reactions due to its short half life
• Fluoxetine can cause agitation and anxiety, but it has fewer discontinuation reactions due to its long half life
• Sertraline has been associated with a higher incidence of diarrhoea than other SSRIs
The risk of drug interactions appears to be lower with Citalopram and Sertraline.
Caution with cardiac disease recommended for all classes. Evidence suggests greater toxicity with Tricyclic Antidepressants (TCAs). These are contraindicated immediately after an MI or in patients at risk of arrhythmias. Venlafaxine and Duloxetine are contraindicated in uncontrolled hypertension. SSRIs normalise elevated indices of platelet activation and aggregation seen in non-treated patients with depression and ischaemic heart disease (IHD), which could explain an apparent protective effect. However there is increased risk of gastrointestinal (GI) bleeding. Sertraline is the SSRI of choice with IHD.
SSRIs are considered first-line. TCAs and Monoamine Oxidase Inhibitors (MOAIs) should be avoided if possible due to their effect on weight and glucose homeostasis.
SSRIs are first choice, but should be discontinued if epilepsy control is poor or worsens on treatment.
Pregnancy and lactation
Antidepressants should only be used in pregnancy if the benefits outweigh the risks.
TCAs have lowest risk in pregnancy. Most data is available for Amitriptyline and Imipramine.
In breast feeding Imipramine and Nortriptyline are preferred as they are present in low levels in breast milk.
By comparison to other classes, SSRI antidepressants have low toxicity in overdose. However, fatalities can occur with a drug overdose from any class. Dosulepin is particularly toxic in overdose. Its use is no longer recommended. There is little data in relation to Duloxetine. However, fatalities have occurred with both mixed and single overdoses of this drug.
The patient should be informed of;
- The reasons for starting the medication
- The importance of taking it,
- Possible side effects
- Possible discontinuation effects
- And that treatment can take between two and four weeks to take effect
A starting dose should be used and titrated. However, for some SSRIs, Mirtazapine, Moclobemide, Reboxetine and Venlafaxine the starting dose may be effective and titration may not be necessary.
Monitoring and follow up
Patients should be seen after two weeks or sooner, and then every two to four weeks to monitor response to treatment and watch for suicidal ideation (particular risk in younger patients).
Continue treatment for at least four weeks before increasing the dose or switching to an alternative antidepressant.
Patients should continue therapy for six to nine months after recovery from a single episode.
Relapse after a single episode is common. 50- 80% will have a second episode and 80-90% of these will have a third. NICE recommends that for those who have had two or more episodes with significant functional impairment maintenance treatment should be continued for at least two years. Thereafter, long term treatment should be reviewed every two years.
For those patients who do not respond to treatment it is important to review diagnosis and check compliance. Evidence for effectiveness of switching to an alternative anti-depressant is weak. However, NICE do recommend switching to an alternative drug if the patient does not improve on the initial treatment.
Abrupt cessation should be avoided and gradual tapering is preferred. However, for some drugs a 'washout period' is required and details of individual drug interactions should always be checked. Particular care should be taken when switching to or from MAOIs or fluoxetine.
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