Depression Antidepressant Update
| Key messages on the use of antidepressants effectiveness, choice, optimising response, dose and duration, switching |
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| Venlafaxine: how and when to use | |
| Antidepressants for elderly people | |
| Antidepressants in pregnancy and breastfeeding | |
| Suicide and antidepressants | |
| References | |
| Issue 1 contents |
Full colour PDF of the pages as they appeared in ‘best practice’.
Printer frendly PDF.
Key messages on the use of antidepressants
- Clinical response to antidepressants should be assessed by an adequate trial, i.e. appropriate dose for at least 4 – 6 weeks.
- It is often possible to manage adverse effects before switching treatment, e.g. dose reduction in anxiety.
- The basis for drug selection is multifactorial including the drug’s adverse effect profile, potential for drug interactions, concurrent medical conditions, safety in overdose, and previous response to treatment (in the case of recurrent depression).
- SSRIs are usually the first choice antidepressant in older people but specific adverse effects and drug interactions require monitoring.
- Venlafaxine is a useful third line antidepressant which can be tried if there has been an unsatisfactory response to an adequate trial of two other antidepressants. Special authority is required.
- Venlafaxine can cause adverse cardiovascular effects. Patients should be assessed for cardiac risk before and during treatment.
- TCAs are considered relatively safe in pregnancy. There have been recent concerns over a possible link between congenital anomalies and first trimester exposure to paroxetine and perhaps other adverse outcomes of pregnancy with other SSRIs. Citalopram provides lower infant drug exposure than fluoxetine during breastfeeding.
- It is very important to identify and address key stressors and triggers for depression and to assess the risk of suicide and harm to others.
Effectiveness of antidepressants in treatment of depression in primary care
In mild depression the evidence for effectiveness of drug treatment is relatively weak and non-drug treatments should be considered first line. In moderate to severe depression, antidepressants have proven clinical effectiveness but individual response to antidepressants varies and only about 50% of patients respond to the first drug chosen. Most efficacy trials are based on response (i.e. improvement) not remission and residual symptoms are possible even after 6 weeks. In most patients residual symptoms (often reflecting continuation of underlying stressors) can be expected and should be actively managed.
Choice of antidepressant
There is no compelling evidence that one drug or drug group is more effective or better tolerated than another so choice of antidepressant is based on individual patient factors and includes:
- Previous response. If a patient has responded well to an antidepressant before, consider that drug as first choice.
- Adverse effects. Avoid drugs which have previously caused troublesome or unmanageable adverse effects. Consider the drug’s adverse effect profile and its potential for aggravating any concurrent conditions. For example, avoid TCAs in cardiac conduction abnormalities.
- Assess the potential for drug interactions. For example, citalopram has a much lower potential for interactions than fluoxetine or venlafaxine.
- Individual tolerance to adverse effects. For some people the anticholinergic effects of TCAs will be unacceptable but others will not tolerate the stimulatory effects sometimes associated with SSRIs.
- Co-morbid psychiatric or medical conditions may influence drug choice.
- Compliance and concordance. If a person’s drug taking is erratic and unreliable, fluoxetine may be a better choice than paroxetine as it has a long half-life and is less likely to cause discontinuation effects.
- Suicide risk. The potential for fatal overdose is much higher with TCAs than with SSRIs. Suicidal thinking has been linked to SSRIs but this can also occur with TCAs and any antidepressant drug treatment.
Optimising response
Optimising the response to antidepressant treatment involves initial drug choice as outlined above, use of an adequate dose for sufficient duration, management of adverse effects, review of diagnosis, management of patient expectations and the use of concurrent non-drug treatment. It is very important to explain to patients the possibility of non-drug options to augment antidepressants and the expectations of antidepressant therapy. A person’s expectations and beliefs about their condition and treatments can influence compliance.
Appropriate dose and duration
Antidepressants should usually be started at the recommended initial dose and the response reviewed after 4 - 6 weeks. With TCAs, gradual titration every 3 - 7 days is generally recommended to assess tolerance of dose related side effects. A smaller initial dose should be considered in some situations, e.g. if there is associated panic disorder or anxiety or if the person has previously found drug treatment intolerable.
If response to an antidepressant is poor, partial or not sustained after 4 - 6 weeks, check the compliance and review the diagnosis before considering a change. Some patients may respond to an increase in dose according to the manufacturer’s recommendations. Temporary dose reduction to manage adverse effects may be warranted. For example, if an SSRI causes initial mild restlessness (not associated with severe anxiety or suicidal ideation), reducing the dose or short term use of a benzodiazepine may be effective instead of switching to an alternative drug.
Switching drug therapy
If there is a partial response, or an initial response that has become attenuated, a further increase in dose may be effective. If there is no response at all to the usual maximum dose then a response may be obtained by changing to another drug.
There are no hard and fast rules to guide which drug to switch to. Similar factors that governed the initial drug choice may be relevant and there may be some logic in trying a drug from a different class. However, a response or better tolerability is often seen by changing to another drug from the same class, (e.g. switching from fluoxetine to citalopram). This may be explained by subtle differences in pharmacology or differences in drug metabolism and genetic polymorphism. (See article on pharmacogenetics). When switching drugs, consider the need for washout periods and cross tapering and the management of discontinuation syndrome. (bpacnz, 2004).
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