Medication

Medication that relieves the symptoms of depression has been available for several decades. Typical first-line therapy for depression is the use of a selective serotonin reuptake inhibitor, such as citalopram (Celexa), fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft). Under some circumstances, medication and psychotherapy may be more effective than either treatment separately.[32]

Selective serotonin reuptake inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) are a family of antidepressants considered to be the current standard of drug treatment. It is thought that one 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 by the presynaptic nerve, thus maintaining higher levels of 5-HT in the synapse. Recently, however, two researchers demonstrated that the advertised connection between serotonin deficiency and symptoms of depression is a marketing technique rather than a scientific portrayal of how the drugs actually work.[33] Recent research indicates that these drugs may interact with transcription factors known as "clock genes",[34] which may be important for the addictive properties of drugs of abuse and possibly in obesity.[35][36]

Recent randomized controlled trials in Archives of General Psychiatry showed that up to one-third of effects of SSRI Treatment can be seen in first week. Early effects also shown to have secondary effect of reducing absolute reduction in HDRS score by 50 percent. Even more recent studies, published by the Archives of General Psychiatry note that 25% of so-called clinical depression does not meet a disease criteria and should be considered to be ordinary sadness and adjustment to the difficulties in life.

This family of drugs includes fluoxetine (Prozac), paroxetine (Paxil), escitalopram (Lexapro), citalopram (Celexa), and sertraline (Zoloft). These antidepressants typically have fewer adverse side effects than the tricyclics or the MAOIs, although such effects as drowsiness, dry mouth, nervousness, anxiety, insomnia, decreased appetite, 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. Though safer than first generation antidepressants, SSRI's may not work as often, suggesting the role of norepinephrine. However, it should be noted that all psycho-active medications extend the reaction time, thus increasing the likelihood of falls and road crashes.

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor) and duloxetine (Cymbalta) are a newer form of antidepressant that works on both norepinephrine and 5-HT. They typically have similar side effects to the SSRIs, although there may be a withdrawal syndrome on discontinuation that may necessitate dosage tapering.

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 minimizing serotonin related side-effects by blocking certain serotonin receptors. The only example of this class in clinical use is mirtazapine (Avanza, Zispin, Remeron).

Norepinephrine (noradrenaline) reuptake inhibitors (NRIs)

Norepinephrine (noradrenaline) reuptake inhibitors (NRIs) such as reboxetine (Edronax) act via norepinephrine (also known as noradrenaline). NRIs are thought to have a positive effect on concentration and motivation in particular, though they have been known to increase aggression.

Norepinephrine-dopamine reuptake inhibitors

Norepinephrine-dopamine reuptake inhibitors such as bupropion (Wellbutrin, Zyban) inhibit the neuronal reuptake of dopamine and norepinephrine (noradrenaline).[37]

Tricyclic antidepressants (TCAs)

Tricyclic antidepressants are the oldest and include such medications as amitriptyline and desipramine. 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. Several 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. However, tricyclic antidepressants are still used because of their high potency, especially in severe cases of clinical depression.

Monoamine oxidase inhibitor (MAOIs)

Monoamine oxidase inhibitors (MAOIs) such as phenelzine (Nardil) may be used if other antidepressant medications are ineffective. 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. MAOIs work by blocking the enzyme monoamine oxidase which breaks down the neurotransmitters dopamine, serotonin, and norepinephrine (noradrenaline). MAOIs can be as effective as tricyclic antidepressants, although they can have a higher incidence of dangerous side effects (as a result of inhibition of cytochrome P450 in the liver). A new generation of MAOIs has been introduced; moclobemide (Manerix), known as a reversible inhibitor of monoamine oxidase A (RIMA), acts in a more short-lived and selective manner and does not require a special diet. Additionally, Emsam is a classic MAOI (selegiline) delivered through a transdermal patch, so as to avoid interactions in the digestive tract that otherwise occur when delivered orally.

Augmentor drugs

Some antidepressants have been found to work more effectively in some patients when used in combination with another drug. Such "augmentor" drugs include tryptophan (Tryptan) and buspirone (Buspar).

Tranquillizers and sedatives, typically the benzodiazepines, may be prescribed to ease anxiety and promote sleep. Because of their high potential for fostering dependence, these medications are intended only for short-term or occasional use. Medications often are used not for their primary function but to exploit what are normally side effects. Quetiapine fumarate (Seroquel) is designed primarily to treat schizophrenia and bipolar disorder, but a frequently reported side-effect is somnolence. Therefore, this drug can be used in place of an antianxiety agent such as clonazepam (Klonopin, Rivotril).

Antipsychotics such as risperidone (Risperdal), olanzapine (Zyprexa), and Quetiapine (Seroquel) are prescribed as mood stabilizers and are also effective in treating anxiety. Their use as mood stabilizers is a recent phenomenon and is controversial with some patients. Antipsychotics (typical or atypical) may also be prescribed in an attempt to augment an antidepressant, to make antidepressant blood concentration higher, or to relieve psychotic or paranoid symptoms often accompanying clinical depression. However, they may have serious side effects, particularly at high dosages, which may include blurred vision, muscle spasms, restlessness, tardive dyskinesia, and weight gain.

Antidepressants by their nature behave similarly to psychostimulants. Antianxiety medications by their nature are depressants. Close medical supervision is critical to proper treatment if a patient presents with both illnesses because the medications tend to work against each other.

Psycho-stimulants 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 which are common in atypical depression can be quickly resolved with the addition of low to moderate dosages of amphetamine or methylphenidate (brand names Adderall and Ritalin, respectively)as these chemicals enhance motivation and social behavior, as well as suppress appetite and sleep. These chemicals are also known to restore sex drive. Extreme caution must be used however with certain populations. Stimulants are known to trigger manic episodes in people suffering from bipolar disorder. They are also easily abused as they are effective substitutes for Methamphetamine when used recreationally. 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, and nausea or diarrhea. Some of the anticonvulsants, such as carbamazepine (Tegretol), sodium valproate (Epilim), and lamotrigine (Lamictal), are also used as mood stabilizers, particularly in bipolar disorder.

Medication failure

Approximately 30% of patients have remission of depression with medications.[38] For patients with inadequate response, either adding sustained-release bupropion(initially 200 mg per day then increase by 100 mg up to total of 400 mg per day) or buspirone (up to 60 mg per day) for augmentation as a second drug can cause remission in approximately 30% of patients[39], while switching medications can achieve remission in about 25% of patients.[40]