Antidepressants

• What are antidepressants?
• What are antidepressants used for?
• Drug treatment
  • Serotonin syndrome
• Precautions when taking antidepressants
  • Pregnancy and the post-natal period
  • Elderly
  • Children and adolescents
  • Interaction with other medicines

What are antidepressants?

Antidepressants are a class of drug which act to relieve the symptoms of depression by elevating noradrenaline, serotonin and dopamine levels in the body which may be described as the “happy” chemicals in the body. There are many different kinds of antidepressants including:

• Monoamine oxidase inhibitors [MAOIs] (phenelzine, tranylcypromine)
• Selective serotonin reuptake inhibitors [SSRIs] (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline)
• Tricyclic antidepressants [TCAs] (amitriptyline, clomipramine, dothiepin, doxepin, imipramine, nortriptyline, trimipramine)
• Other antidepressants (mianserin, mirtazepine, moclobemide, reboxetine, venlafaxine).

What are antidepressants used for?

Antidepressants are used for:

• Moderate to severe depressive illness
• Anxiety
• Obsessive compulsive disorders
• Eating disorders
• Chronic pain

Drug treatment

Before commencing treatment organic causes such as alcohol and illicit drug misuse, corticosteroid use, hypothyroidism (insufficient production of thyroid hormone by your thyroid gland) may be excluded by your doctor. Your doctor may perform a structured assessment tool in order to document the extent and nature of your signs and symptoms for later assessment of treatment efficacy.

Your doctor may commence treatment when the diagnostic criteria for depression have been fulfilled for more than 2 weeks. The diagnostic criteria for major depression is as such- Depressed mood (or irritable mood in children) and/or significant loss of interest or pleasure with at least four of the following:

• marked alteration in weight or appetite
• insomnia or hypersomnia nearly every day
• Psychomotor agitation or retardation nearly every day
• fatigue or loss of energy

Your doctor will take several factors into consideration before deciding which antidepressant is best for you. Such factors include:

• Your previous response to antidepressant therapy
• Concurrent medical and psychiatric therapy such as bipolar disorder
• Possibility for drug interactions
• Adverse effect profile of the agent eg SSRIs stimulating effects may be useful when hypersomnia (recurrent episodes of excessive daytime sleepiness or prolonged night time sleep) is a presenting symptom
• Probability that the patient will attempt a intentional overdose and the toxicity of the agent in overdose

All antidepressants have approximately equal efficiency however individual patients tend to respond differently to different agents. Although the antidepressant classes posses diverse adverse effect profiles, no classes is superior in terms of tolerability and hence most agents can be used as as part of the initial treatment.

Inital treatment options: TCAs, SSRIs, controlled release venlafaxine, mirtazepine and moclobemide are all considered as first line drugs in adults.

If initial treatment options are not successful: Non-selective MOAIs are generally considered as second line agents and a preferably initiated by a psychiatrist.

If at the early stage of depression you suffer from insomnia or other ailments your doctor may prescribe other medications to treat such symptoms.

Serotonin syndrome

Serotonin syndrome is a side effect of antidepressants and may arise from:

• A high dose of a single drug
• When more than one serotonergic agents are used together
• When altering antidepressants without an adequate washout period between drugs

Serotonin concentration rises thus over stimulating the serotonin receptors resulting in:

• Mental state changes such as confusion, hypomania (irritable mood), agitation
• Myoclonus/clonus (involuntary muscle contractions), hyperreflexia, tremor, incoordination
• Shivering, sweating, fever
• Diarrhoea

Serotonin syndrome may arise due to several drugs including the antidepressants. Always inform your doctor if you experience any of the above symptoms.

Precautions when taking antidepressants

Pregnancy and the post natal period

Treatment of depression during this time is complex and requires careful analysis of the risk to both the mother and infant by the doctor. Current evidence suggests that the TCAs and SSRIs (except paroxetine) are relatively safe. Normally the lowest effective dose will be used. There is some evidence that infants of mothers whom take antidepressants may experience some withdrawal symptoms but this is usually self limiting. Such infants may require careful observation for a few days in order to identify and, if necessary, treat such symptoms.

If you are already on antidepressant medication and are pregnant or planning to become pregnant please seek your doctors advice.

Elderly

The elderly may respond more slowly to antidepressants therapy.

Children and adolescents

Antidepressants are usually not used for initial treatment and are typically used in combination with non-drug therapy. Other diseases are common in children with depression and will be managed by your doctor.

Interaction with other medicines

Antidepressant medication can interact with other medicines. Your doctor may try and avoid the combination or monitor you. If you have any concerns talk to your doctor about them.

References

1. Lazo J, Gilman A, Brunton L, Parker K. Goodman and Gilman’s the pharmacological basis of therapeutics. 11th ed. New York: McGraw-Hill; 2005.
2. Australian Medicines Handbook 2006, Adelaide, Pharmaceutical society of Australia, 2006.
3. Smith AJ, Sketris I et al. A comparison of antidepressant use in Nova Scotia, Canada and Australia. Pharmacoepidemiology and Drug Safety 2008; DOI: 10.1002/pds.
4. Lee M-S The Pharmacogenetics of Antidepressant Treatments for Depressive Disorders. Drug Development Research 2005 65:170-178.
5. Swaby HE A Review of Pregnancy Outcome Following Exposure to Newer Antidepressants[online] August 1995 Available from: URL:http://www.antidepressantsfacts.com/review-pregnancy-ssri.htm
6. Giron MST, Fastbom J and Winblad B Clincial trials of potential antidepressants: to what extent are the elderly represented: a review. International Journal of Geriatric Psychiatry 2005; 20: 201-217.
7. Adverse Drug Reactions Advisory Committee. Use of SSRI antidepressants in children and adolescents [online] Available from: URL: http://www.tga.gov.au/adr/adrac_ssri.htm 15 October 2005.
8. Hoogendijk WJG, Lieverse R and Beekman ATF Suicide Risk and Antidepressants: Beyond the Controversy Drug Development Research 2005 65: 179-184.
9. Dean AJ, Hendy A and McGuire T Antidepressants in children and adolescents-changes in utilisation after safety warnings Pharmacoepidemiology and Drug Safety 2007 16: 1048-1053.
10. Wells BG, DiPiro JT, Schwinghammer TL, Hamilton CW Pharmacotherapy Handbook. 6th Edition. McGraw-Hill: USA 2006.

Further reading
Electronic APP Guide (eAPP Guide), 2007.