Selective serotonin reuptake inhibitors (SSRIs)
Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants considered the current standard of drug treatment. A possible cause of depression is an inadequate amount of serotonin, a chemical used in the brain to transmit signals between neurons. SSRIs are said to work by preventing the reuptake of serotonin (also known as 5-hydroxytryptamine, or 5-HT) by the presynaptic neuron, thus maintaining higher levels of 5-HT in the synapse. Chemists Klaus Schmiegel and Bryan Molloy of Eli Lilly discovered the first SSRI, fluoxetine. Antidepressants List of this class of drugs includes:
- Citalopram (Celexa, Cipramil)
- Escitalopram (Lexapro, Cipralex, Seroplex, Lexamil)
- Fluoxetine (Prozac, Sarafem, Symbyax)
- Fluvoxamine (Luvox)
- Paroxetine (Paxil, Aropax)
- Sertraline (Zoloft)
These antidepressants typically have fewer adverse effects than the tricyclics or the MAOIs, although such effects as drowsiness, dry mouth, nervousness, anxiety, insomnia, decreased appetite, long-term weight gain and decreased ability to function sexually may occur. Some side effects may decrease as a person adjusts to the drug, but other side effects may be persistent.
Work by two researchers has called into question the link between serotonin deficiency and symptoms of depression, noting that the efficacy of SSRIs as treatment does not in itself prove the link. Research indicates that these drugs may interact with transcription factors known as “clock genes”, which may play a role in the addictive properties of drugs (drug abuse), and possibly in obesity.
A systematic review of randomized controlled trials published in the Archives of General Psychiatry showed that up to one-third of the 6-week effect of SSRI Treatment can be seen in the first week. The same study also found that patients treated with SSRIs were 64% more likely to achieve a 50% absolute reduction in HRSD than patients given a placebo.
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a newer form of antidepressant that work on both norepinephrine and 5-HT. They typically have similar side effects to the SSRIs, though there may be a withdrawal syndrome on discontinuation that may necessitate dosage tapering. These include:
- Desvenlafaxine (Pristiq)
- Duloxetine (Cymbalta)
- Milnacipran (Ixel)
- Venlafaxine (Effexor)
Noradrenergic and specific serotonergic antidepressants (NaSSAs)
Noradrenergic and specific serotonergic antidepressants (NaSSAs) form a newer class of antidepressants which purportedly work to increase norepinephrine (noradrenaline) and serotonin neurotransmission by blocking presynaptic alpha-2 adrenergic receptors while at the same time blocking certain serotonin receptors. Side effects may include drowsiness, increased appetite, and weight gain. Examples include:
- Mianserin (Tolvon)
- Mirtazapine (Remeron, Avanza, Zispin)
Norepinephrine (noradrenaline) reuptake inhibitors (NRIs)
Norepinephrine (noradrenaline) reuptake inhibitors (NRIs) act via norepinephrine (also known as noradrenaline). NRIs are thought to have a positive effect on the concentration and motivation in particular. These include:
- Atomoxetine (Strattera)
- Mazindol (Mazanor, Sanorex)
- Reboxetine (Edronax)
- Viloxazine (Vivalan)
Norepinephrine-dopamine reuptake inhibitors (NDRIs)
Norepinephrine-dopamine reuptake inhibitors inhibit the neuronal reuptake of dopamine and norepinephrine (noradrenaline). These include:
- Bupropion (Wellbutrin, Zyban)
Selective serotonin reuptake enhancers (SSREs)
- Tianeptine (Stablon, Coaxil, Tatinol)
Norepinephrine-dopamine disinhibitors (NDDIs)
Norepinephrine-dopamine disinhibitors (NDDIs) act by antagonizing the serotonin 5-HT2C receptor which normally acts to inhibit norepinephrine and dopamine release, thereby promoting outflow of these neurotransmitters.
- Agomelatine (Valdoxan, Melitor, Thymanax)
Tricyclic antidepressants (TCAs)
Tricyclic antidepressants are the oldest class of antidepressant drugs. Tricyclics block the reuptake of certain neurotransmitters such as norepinephrine (noradrenaline) and serotonin. They are used less commonly now due to the development of more selective and safer drugs. Side effects include increased heart rate, drowsiness, dry mouth, constipation, urinary retention, blurred vision, dizziness, confusion, and sexual dysfunction. Toxicity occurs at approximately ten times normal dosages; these drugs are often lethal in overdoses, as they may cause a fatal arrhythmia. However, tricyclic antidepressants are still used because of their effectiveness, especially in severe cases of major depression. These include:
Tertiary amine tricyclic antidepressants:
- Amitriptyline (Elavil, Endep)
- Clomipramine (Anafranil)
- Doxepin (Adapin, Sinequan)
- Imipramine (Tofranil)
- Trimipramine (Surmontil)
Secondary amine tricyclic antidepressants
- Desipramine (Norpramin)
- Nortriptyline (Pamelor, Aventyl, Noritren)
- Protriptyline (Vivactil)
Monoamine oxidase inhibitor (MAOIs)
Monoamine oxidase inhibitors (MAOIs) may be used if other antidepressant medications are ineffective. MAOIs work by blocking the enzyme monoamine oxidase which breaks down the neurotransmitters dopamine, serotonin, and norepinephrine (noradrenaline). Because there are potentially fatal interactions between this class of medication and certain foods (particularly those containing tyramine), as well as certain drugs, classic MAOIs are rarely prescribed anymore. However, this does not apply to Emsam, the transdermal patch form of selegiline, which due to its bypassing of the stomach has a lesser propensity to induce such events. MAOIs can be as effective as tricyclic antidepressants, although they are generally used less frequently because they have a higher incidence of dangerous side effects and interactions. A new generation of MAOIs has been introduced; moclobemide (Manerix), known as areversible inhibitor of monoamine oxidase A (RIMA), acts in a more short-lived and selective manner and does not require a special diet. The MAOI group of medicines include:
- Isocarboxazid (Marplan)
- Moclobemide (Aurorix, Manerix)
- Phenelzine (Nardil)
- Selegiline (Eldepryl, Emsam)
- Tranylcypromine (Parnate)
Some antidepressants have been found to work better in some patients when used in combination with another drug. Such “augmenter” drugs include:
- Buspirone (Buspar)
- Gepirone (Ariza)
- Nefazodone (Serzone)
- Tandospirone (Sediel)
- Trazodone (Desyrel)
- Bupropion (Wellbutrin/Zyban)
Tranquillizers and sedatives, typically the benzodiazepines, are prescribed to ease anxiety and promote sleep. Because of the high risk of dependency, these medications are intended only for short-term or occasional use. Medications are often used not for their primary functions, but to exploit what are normally side effects. Quetiapine fumarate (Seroquel) is designed primarily to treat schizophrenia and bipolar disorder, but frequently causes somnolence because of its affinity for histamine (H1 and H2) receptors, exploiting the same side effects asdiphenhydramine (Benadryl).
Antipsychotics such as risperidone (Risperdal), olanzapine (Zyprexa), and quetiapine (Seroquel) are prescribed as mood stabilizers and to treat anxiety. Their use as mood stabilizers is a recent phenomenon, and controversial among some patients. Antipsychotics, whether typical or atypical, may also be prescribed to augment an antidepressant, to increase the blood concentration of another drug, or to relieve the psychotic or paranoid symptoms that often accompany clinical depression. However, they can cause serious side effects, particularly at high dosages, including blurred vision, muscle spasms, restlessness, tardive dyskinesia, and weight gain.
Psychostimulants are sometimes added to an antidepressant regimen if the patient suffers from anhedonia, hypersomnia and/or excessive eating as well as low motivation. These symptoms are common in atypical depression, and can be resolved by adding low to moderate doses of amphetamine (Adderall), methylphenidate (Ritalin) or modafinil (Provigil, Alertec), as these chemicals can enhance motivation and social behavior, and suppress appetite and sleep. Modafinil is unique in its effect on sleep: it increases alertness and reduces drowsiness while the patient is active, but does not inhibit normal sleep. These medications can also restore sexual drive, although this is a negative side effect and not a reason for the prescription of psychostimulants. Extreme caution must be used however with certain populations. Stimulants are known to trigger manic episodes in people suffering from bipolar disorder. Close supervision of those with substance abuse disorders is urged. Emotionally labile patients should avoid stimulants, as they exacerbate mood shifting.
Lithium remains the standard treatment for bipolar disorder and is often used in conjunction with other medications, depending on whether mania or depression is being treated. Lithium’s potential side effects include thirst, tremors, light-headedness, nausea, and diarrhea. Some of the anticonvulsants, such as carbamazepine (Tegretol), sodium valproate (Epilim), andlamotrigine (Lamictal), are also used as mood stabilizers, particularly in bipolar disorder. Both lithium and lamotrigine have also been studied and used to augment antidepressants in treatment-resistant unipolar depression.
More info at: Antidepressants List