Antidepressants are drugs and herbs used to treat depression and anxiety disorders; overall, on average, they are twice as likely as a placebo to alleviate depression in clinical trials, they are usually reserved for moderate-severe cases of depression, although St. John's wort, low-dose flupentixol or amisulpride may be used in mild cases of depression. They usually take weeks to kick in, hence it is important for people not to get disappointed if they do not see an immediate effect as this is to be expected.
Abbreviations and acronymsEdit
- MAOIs: monoamine oxidase inhibitors.
- NaSSAs: Noradrenergic and specific serotonergic antidepressant.
- NDRIs: noradrenaline-dopamine reuptake inhibitors.
- NRIs: noradrenaline reuptake inhibitors.
- RIMAs: reversible inhibitors of monoamine oxidase A.
- SARIs: Serotonin antagonist and reuptake inhibitors.
- SJW: St. John's wort; scientific name: Hypericum perforatum.
- SNRIs: serotonin-noradrenaline reuptake inhibitors.
- SSRIs: selective serotonin reuptake inhibitors.
- TCAs: tricyclic antidepressants.
Abbreviated list of agentsEdit
Reuptake inhibitors, including:[note 1]
- NDRIs such as bupropion (Prexaton, Wellbutrin, Zyban).
- NRIs such as reboxetine (Edronax, Prolift) and viloxazine (Vicilan, Vivalan, Vivarint).
- SNRIs such as desvenlafaxine (Pristiq), duloxetine (Cymbalta, Yentreve), levomilnacipran (Fetzima), milnacipran (Ixel, Savella) and venlafaxine (Efexor, Effexor).
- SSRIs such as citalopram (Celexa, Cipramil), escitalopram (Cipralex, Lexapro), fluoxetine (Lovan, Prozac), fluvoxamine (Faverin, Luvox, Movox, Voxam), paroxetine (Aropax, Extine, Paxil, Paxtine, Seroxat) and sertraline (Eleva, Lustral, Sertra, Sertracor, Setrona, Xydep, Zoloft).
- TCAs such as amitriptyline (Elavil, Endep), amoxapine (Asendin, Asendis), clomipramine (Anafranil, Placil), desipramine (Norpramin, Pertofran), dosulepin (Australian generic name: Dothiepin; brand names: Dothep, Prepadin, Prothiaden), doxepin (Deptran, Prudoxin, Silenor, Sinepan, Sinequan, Xepin, Zonalon), imipramine (Tofranil, Tolerade), lofepramine (Emdalin, Gamanil, Lomont), maprotiline (Ludiomil), nortriptyline (Allegron, Aventyl, Norpress, Pamelor) and trimipramine (Surmontil).
- Irreversible inhibitors, including: iproniazid (Marsilid), isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Emsam), and tranylcypromine (Parnate).
- Reversible inhibitors of monoamine oxidase A, including: brofaromine (Consonar), moclobemide (Aurorix, Manerix) and pirlindole (Implementor, Normazidol, Pyrazidol).
Receptor modulators such as:[note 3]
- NaSSAs: mianserin (Lumin, Tolvon), mirtazapine (Avanza, Axit, Remeron) and setiptiline (Tecipul).
- SARIs: nefazodone (Deprefax, Dutonin, Serzone) and trazodone (Desyrel, Molipaxin, Oleptro, Trialodine, Trittico).
Mechanism of actionEdit
Their mechanisms vary considerably but they usually work by increasing[note 4] monoamine[note 5] concentrations or activity[note 6] in the brain. There are three major types of antidepressant, based on their pharmacology: monoamine oxidase inhibitors, reuptake inhibitors or receptor modulators (either agonists or antagonists).[note 7]
Choice of antidepressantEdit
Usually when a physician is considering which antidepressant to prescribe usually they base their decision based on five major variables:
- Their patient's particular subtype of depression or anxiety disorder
- Their patient's age, gender, socioeconomic status, lifestyle (e.g., whether they are physically active), relationship status, etc.
- Their patient's medical history (both personal and family), including medications they are currently on and pre-existing conditions or addictions (like cigarette smoking).
- Their patient's risk for suicide.
- Their patient's likelihood for compliance.
Type of depressionEdit
Their subtype of depression basically refers to whether or not they have melancholic features, psychotic features, atypical features, etc. These different subtypes are explained here. Melancholic depression usually responds best to tricyclic antidepressants (TCAs), although these agents have their limitations (mostly due to side effects and toxicity in overdose; more patients quit taking these agents than with the more recently introduced agents). Psychotic depression usually responds best to an atypical antipsychotic combined with an antidepressant (e.g., olanzapine with fluoxetine), although ECT may also be used, especially in those at high risk for suicide, but it is known to cause memory problems. Atypical depression usually responds best to monoamine oxidase inhibitors, although these agents are limited by food and drug interactions and side effects (in fact it is one of the agents associated with the highest proportion of patients discontinuing due to side effects, along with the TCAs). Bipolar depression usually responds best to quetiapine (an atypical antipsychotic limited by side effects of drowsiness, weight gain [at about 1.76 kg/month], constipation, dry mouth, memory problems and the fact it may increase one's risk for developing diabetes mellitus), olanzapine in combination with fluoxetine (also subject to the side effects listed for quetiapine), lurasidone (another atypical antipsychotic; not available in Australia or the U.K., yet), lamotrigine (an anti-seizure medicine; usually started by a psychiatrist as it can cause potentially fatal skin rashes if the doses are increased too rapidly) or a monoamine oxidase inhibitor. Mild depression tends to respond best to St. John's wort, the talking approach or low-dose flupentixol/amisulpride.
Their age influences the choice of antidepressant due to a few different reasons; for one, the elderly are usually more prone to falls and hence any medication that has a risk of causing orthostatic hypotension[note 8] is usually avoided (which includes the MAOIs, some atypical antidepressants and TCAs). Secondly women/girls of childbearing potential (that is, those under the age of 40 and at least 12) are usually advised to avoid paroxetine or clomipramine as they could cause heart defects.
Sexual side effectsEdit
Adolescents and those in their twenties are also likely to be sexually active, or at least wish to be one day and in these patients agents with a high risk of causing sexual side effects (like the SSRIs and SNRIs) are usually best avoided. But in this patient population there is also a higher risk of suicide during the early phase of antidepressant treatment, hence agents with a higher toxicity in cases of overdose are usually avoided (like the TCAs, iMAOIs), hence leaving the SSRIs like escitalopram, fluoxetine and sertraline as first-choice agents (all three of which have a high risk of causing sexual side effects). Older patients may also have a higher risk for suicide.
Their sex influences which agent they are prescribed as clomipramine and paroxetine could cause birth defects, as earlier mentioned, hence female patients are less likely to be prescribed these agents if they are of child-bearing potential.
For patients at a high risk for suicide[note 9] the antidepressant prescribed usually is one that is less toxic in cases of overdose (such as the selective serotonin reuptake inhibitors or atypical antidepressants).
One's medical history is also relevant as many antidepressants have numerous drug interactions, hence may interact with prescription (Rx) and over-the-counter (OTC) medicines.
For example, in patients prescribed Rx medicines that reduce the seizure threshold (that is, those that make one more likely to experience a seizure) like bupropion (a medicine to help smokers quit) usually the SSRIs or moclobemide are the best choice, as they have minimal effects on the seizure threshold. Likewise those with epilepsy are probably best treated with SSRIs or moclobemide, although if they are prescribed an anticonvulsant (anti-seizure medicine) another agent may be preferred, due to the potential for pharmacokinetic interactions.
Certain pain medications such as pethidine (meperidine in the U.S.A., U.S.A. brand name: Demerol; seldom used nowadays), tapentadol and tramadol can also provoke a serotonin syndrome in patients receiving serotonergic antidepressants like the SSRIs, SNRIs, TCAs and MAOIs. Many SSRIs inhibit various drug-metabolizing enzymes too, hence several pharmacokinetic interactions if the patient is already taking another medicine. OTC/Rx painkillers/anti-inflammatory drugs like the NSAIDs are also known to increase one's risk for bleeds in the digestive tract, hence agents like the SSRIs and venlafaxine that are known to increase the risk of upper GI bleeds are best avoided. Physicians are also often slow to prescribe the SSRIs or venlafaxine to those with pre-existing stomach ulcers, a history of stomach ulcers or other risk factors for developing stomach ulcers.
Family history of BPDEdit
People with a first-degree relative[note 10] that has bipolar disorder (BPD) are also at a heightened risk for developing bipolar disorder themselves, hence it is often preferable for them to be prescribed an agent with a lower potential for provoking mania like bupropion[note 11] or SSRIs. Especially seeing how depression is often the first major mood episode experienced by bipolar patients.
The obese or those with a family history of obesity are often prescribed agents that are more stimulating and less prone to cause weight gain (that is, those that wake you up) like bupropion, moclobemide, SNRIs, fluoxetine or sertraline. Likewise the agents that are more prone to cause weight gain (like mianserin, mirtazapine, TCAs, paroxetine, etc.) are likely avoided in those that are physically inactive too.
Patients that are unlikely to be compliant with their medications are often treated with agents that can be withdrawn without withdrawal effects (like fluoxetine or St. John's wort) and are not subject to the requirement of regular blood tests (examples of those that do NOT fit this category include agomelatine and mianserin). Over all the SSRIs citalopram, escitalopram and sertraline, the NDRI bupropion, the RIMA moclobemide,[note 12] St. John's wort, the TCAs lofepramine and tianeptine[note 13] and agomelatine are associated with the lowest rates of discontinuation due to side effects are associated with them. SNRIs are more likely to cause discontinuation due to side effects, as is reboxetine, fluvoxamine and mirtazapine.
Agomelatine is likely to be avoided in people that drink to excess, as is mianserin, mirtazapine, trazodone, nefazodone and tricyclic antidepressants for one of two reasons. For agomelatine and nefazodone it is because of the potential for liver damage that can be triggered from agomelatine/nefazodone treatment to be exacerbated by concurrent alcohol abuse. Mianserin, mirtazapine, trazodone and TCAs are often sedating, hence could add to the sedating effects of alcohol, hence increasing the potential for complications.
Bupropion and nortriptyline are likely to be favoured whenever the patient is a smoker, as they are both known to improve abstinence rates. Desipramine (which, by the way, is not available for use in Australia or the U.K. any more as it is uniquely toxic in cases of overdose) is also more likely to be used in cocaine addicts as it might improve abstinence rates.
- NCBI Bookshelf provides free book resources on this topic.
- PubMed provides review articles from the past five years (limit to free review articles or to systematic reviews)
- The TRIP database provides clinical publications about evidence-based medicine.
- ↑ In brackets are brand names
- ↑ In brackets are brand names
- ↑ In brackets are brand names
- ↑ Or decreasing in the case of tianeptine
- ↑ Namely serotonin, noradrenaline, dopamine and/or melatonin
- ↑ Via interacting directly with their respective receptors
- ↑ There is sometimes some overlap between the different categories
- ↑ A drop in blood pressure that occurs upon standing up, leading to dizziness
- ↑ Such as those with psychotic features, older patients, males, accompanying anxiety, agitation, stress, being widowed or divorced, unexplained weight loss, having a plan in place, lack of reason not to commit suicide.
- ↑ Parent, sibling or child
- ↑ This agent is not available in Australia, New Zealand or the U.K. for this indication; rather it is solely approved to help smokers quit. In the U.S.A., Canada, Spain, Germany and many other developed countries, however, it is approved for this use
- ↑ Although this agent is usually reserved as a second-line treatment due to potential food/drug interactions and its twice-thrice-daily dosing.
- ↑ Neither of which are available in Australia or the U.S.A.; lofepramine is available in the U.K., however
- ↑ 1.0 1.1 Taylor, D; Paton, C; Shitij, K (2012). Maudsley Prescribing Guidelines in Psychiatry (11th ed.). West Sussex: Wiley-Blackwell. ISBN 978-0-47-097948-8.
- ↑ 2.0 2.1 National Collaborating Centre for Mental Health (2010). Depression: the NICE guideline on the treatment and management of depression in adults (PDF) (Updated ed. ed.). London, UK: Royal College of Psychiatrists. ISBN 978-1-904671-85-5. PMID 22132433.
- ↑ Mallinger, AG; Frank, E; Thase, ME; Barwell, MM; Diazgranados, N; Luckenbaugh, DA; Kupfer, DJ (2009). "Revisiting the effectiveness of standard antidepressants in bipolar disorder: are monoamine oxidase inhibitors superior?". Psychopharmacology bulletin 42 (2): 64–74. PMC 3570273. PMID 19629023.
- ↑ 4.0 4.1 Nielsen, RE; Damkier, P (June 2012). "Pharmacological treatment of unipolar depression during pregnancy and breast-feeding--a clinical overview.". Nordic Journal of Psychiatry 66 (3): 159–66. PMID 22283766. doi:10.3109/08039488.2011.650198.
- ↑ Källén, B (July 2007). "The safety of antidepressant drugs during pregnancy.". Expert Opinion on Drug Safety 6 (4): 357–70. PMID 17688379. doi:10.1517/14740322.214.171.1247.
- ↑ Williams, AS (2007). "Antidepressants in pregnancy and breastfeeding". Australian Prescriber (National Prescribing Service) 30 (5): 125–127.
- ↑ White, N; Litovitz, T; Clancy, C (2008 Dec). "Suicidal antidepressant overdoses: a comparative analysis by antidepressant type." (PDF). Journal of Medical Toxicology 4 (4): 238–50. PMC 3550116. PMID 19031375. doi:10.1007/BF03161207. Check date values in:
- ↑ Halverson, JL; Bhalla, RN; Moraille-Bhalla, P; Andrew, LB; Ahmed, I; Aronson, SC; Liskow, BI; Memon, MA; Talavera, F; Walaszek, A (11 August 2014). Bienenfeld, D, ed. "Depression". Medscape Reference. United States: WebMD. Retrieved 15 August 2014.
- ↑ Not available in the U.S.A., however; available in Australia, Canada, New Zealand, Singapore, South Africa and the U.K.
- ↑ Papakostas, GI; Fava, M (October 2006). "A metaanalysis of clinical trials comparing moclobemide with selective serotonin reuptake inhibitors for the treatment of major depressive disorder." (PDF). Canadian Journal of Psychiatry 51 (12): 783–90. PMID 17168253.
- ↑ Cipriani, A; Furukawa, TA; Salanti, G; Geddes, JR; Higgins, JP; Churchill, R; Watanabe, N; Nakagawa, A; Omori, IM; McGuire, H; Tansella, M; Barbui, C (February 2009). "Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis." (PDF). Lancet 373 (9665): 746–58. PMID 19185342. doi:10.1016/S0140-6736(09)60046-5.
- ↑ Hughes, JR; Stead, LF; Hartmann-Boyce, J; Cahill, K; Lancaster, T (January 2014). "Antidepressants for smoking cessation.". The Cochrane Database of Systematic Reviews 1: CD000031. PMID 24402784. doi:10.1002/14651858.CD000031.pub4.
- ↑ Pani, PP; Trogu, E; Vecchi, S; Amato, L (December 2011). "Antidepressants for cocaine dependence and problematic cocaine use.". The Cochrane Database of Systematic Reviews (12): CD002950. PMID 22161371. doi:10.1002/14651858.CD002950.pub3.