Antidepressants
Introduction
Antidepressants are drugs that are used to treat depression. For the purpose of this discussion, antidepressants are categorized as either synthetic or natural. Synthetic antidepressants do not exist in nature and require chemists to synthesize them, government (FDA) approval for human use, and a prescription from a medical doctor (M.D.) to take them. Natural antidepressants occur in nature and generally do not require a prescription. However, as described in the neuroscience basics section, “natural” does not necessarily mean safe and taking any drug without physician approval is never a good idea.
Updated November 17, 2006: List of Synthetic and Natural Antidepressants. Please take the quick poll on the list page so we can determine if there is an interest in illustrations that depict mechanisms of drug action.
Synthetic Antidepressants
Synthetic antidepressants can be divided into groups according to their function (what they do). For the sake of clarity, synthetic antidepressants have been divided into two groups- reuptake inhibitors and monoamine oxidase inhibitors. Reuptake inhibitors are further subdivided into classes that are based on chemical structure (what they look like) and/or molecular mechanisms of action. The chemical structure and representative trade names of each compound can be accessed from the links.
Reuptake inhibitors bind to neurotransmitter transporters and typically increase synaptic levels of serotonin and/or norepinephrine. TCAs (TriCyclic Antidepressants) are an older generation of reuptake inhibitors that were originally named according to their structure. TCAs are composed of three aromatic rings and include imipramine and desipramine. More recently, TCAs have been classified into "tertiary amine TCAs" that affect both serotonin and norepinephrine (e.g. imipramine) and "secondary amine TCAs" that are more specific for norepinerine (e.g. desipramine). Current generation reuptake inhibitors include SSRIs (Selective Serotonin Reuptake Inhibitors) that primarily affect levels of serotonin. SSRI compounds include fluoxetine, fluvoxamine, paroxetine, and sertraline. SSRI-related antidepressants include SNRIs (Serotonin Norepinephine Reuptake Inhibitors) that affect levels of both serotonin and norepinephrine. Venlafaxine and duloxetine are examples of SNRIs. A newer class of antidepressants are termed "atypical" because their mechanisms of action differ from the other classes. Bupropion is an example of an atypical antidepressant that appears to affect both norepinephrine and dopamine.
In contrast to the actions of reuptake inhibitors, monoamine oxidase inhibitors (MAOIs) block the degradation of serotonin, norepinephrine, and dopamine. Monoamine oxidases are enzymes that oxidize neurotransmitters that are located within a cell. Examples of MAOIs include phenelzine and tranylcypromine. In summary, blocking either the reuptake (reuptake inhibitor) or inactivation (MAOI) of neurotransmitters results in increased brain levels of neurotransmitters. Patients need to consult with their physician regarding interactions between medications such as the extreme danger of taking a reuptake inhibitor together with a MAOI.
Related topics:
Pharmacology of SSRI compounds
Molecular mechanisms of antidepressant action
Natural Antidepressants
Plant compounds that are not made by mammals are considered to be unnatural to humans. Furthermore, an excessive amount of a compound that is produced by mammals, although technically natural, has the potential to be extremely toxic. The bottom line is that the term “natural” should be interpreted with caution.
There may be alternatives to synthetic antidepressants, but it is unclear whether they effectively treat depression. The surprising amount of basic research with natural compounds provides a basis to explore the biochemistry of these compounds in greater detail. The most discussed and researched plant with potential antidepressant properties is St. John's wort, or more accurately, an extract of St. John's wort. In simple terms, the plant is ground up using techniques that ultimately generate an extract, which contains many plant components. A hot area of research with St. John's wort involves purifying the individual components of an extract and then performing research studies with the isolated compounds. Great strides have already been accomplished, including the identification of some active components (see active components of St. John's wort). In addition to plant-derived compounds, animal-derived compounds including 5-hydroxytryptophan and S-adenosylmethionine are currently being investigated as potential antidepressants. Other products, particularly plant/herbal extracts, have been touted as antidepressants but their "active" ingredients and mechanisms of action are essentially unknown. Therefore, the related topics are limited to extracts/compounds that have been evaluated in basic research studies and the resulting data published in recognized scientific journals.
Related topics:
Active components of St. John's wort (Hypericum perforatum)
Biochemistry of 5-hydroxytryptophan (5-HTP)
Biochemistry of S-adenosylmethionine (SAM/AdoMet/SAMe/SAM-e)