Depression - Physical treatment

A broad range of physical treatments have been used to help with major depression.

Medication
Antidepressants in general are as effective as psychotherapy; their benefits increase with the severity of the depression, although more patients cease treatment than psychotherapy, likely because of the side effects of antidepressants. A large 2008 meta-analysis of past studies reported that the response to antidepressant treatment in moderate depression were not shown to exceed that of placebo; this interpretation was questioned in an editorial of the British Medical Journal, and a positive but small effect was not ruled out. A black box warning has been introduced in the United States in 2007 on SSRI and other antidepressant medications due to increased risk of suicidality in patients younger than 24.

Selective serotonin reuptake inhibitors (SSRIs), such as sertraline, escitalopram, fluoxetine, paroxetine, and citalopram are the primary medications considered owing to their effectiveness, relatively mild side effects, and because they are less toxic in overdose than other antidepressants. Those who do not respond to one SSRI can be switched to another, which results in improvement in almost 50% of cases. Another option is to switch to the atypical antidepressant bupropion. It is not uncommon for SSRIs to cause or worsen insomnia; the sedating antidepressant mirtazapine can be used in such cases. Venlafaxine, and other serotonin-norepinephrine reuptake inhibitors, may be modestly more effective than SSRIs; however, venlafaxine is not recommended as a first-line treatment because of evidence suggesting its risks may outweigh benefits. Its use is specifically discouraged in children and adolescents. Fluoxetine is the only antidepressant recommended for people under the age of 18 years. Tricyclic antidepressants have more side effects than SSRIs and are usually reserved for the treatment of inpatients, for whom the tricyclic antidepressant amitriptyline, in particular, appears to be more effective. A different class of antidepressants, the monoamine oxidase inhibitors, have historically been plagued by life-threatening adverse effects. They are still used only rarely, although newer and better tolerated agents of this class have been developed.

To find the most effective antidepressant medication with tolerable or fewest side effects, the dosages can be adjusted, and, if necessary, combinations of different classes of antidepressants can be tried. Response rates to the first antidepressant administered may be as low as 50%, and it can take at least six to eight weeks from the start of medication to remission, when the patient is back to their normal self. Antidepressant medication treatment is usually continued for 16 to 20 weeks after remission, to minimise the chance of recurrence. People with chronic depression usually need to take medication for the rest of their lives. The terms refractory depression or treatment-resistant depression are used to describe cases that do not respond to adequate courses of least two antidepressants.

A doctor may add a medication with a different mode of action to bolster the effect of an antidepressant in cases of treatment resistance. Medication with lithium salts has been used to augment antidepressant therapy in those who have failed to respond to antidepressants alone. Furthermore, lithium dramatically decreases the suicide risk in recurrent depression. Addition of a thyroid hormone, triiodothyronine may work as well as lithium, even in patients with normal thyroid function. Addition of atypical antipsychotics when the patient has not responded to an antidepressant is also known to increase the effectiveness of antidepressant drugs, albeit offset by increased side effects.

Electroconvulsive therapy
Electroconvulsive therapy (ECT) is a procedure where pulses of electricity are sent through the brain via two electrodes, usually one on each temple, to induce a seizure while the patient is under a short general anaesthetic. Hospital psychiatrists may recommend ECT for cases of severe major depression which have not responded to antidepressant medication or, less often, psychotherapy or supportive interventions. ECT can have a quicker effect than antidepressant therapy and thus may be the treatment of choice in emergencies such as catatonic depression where the patient has stopped eating and drinking, or where a patient is severely suicidal. ECT is probably more effective than pharmacotherapy for depression in the immediate short-term, although a landmark community-based study found much lower remission rates in routine practice. Used on its own the relapse rate within the first six months is very high; early studies put the rate at around 50%, while a more recent controlled trial found rates of 84% even with placebos. The early relapse rate may be reduced by the use of psychiatric medications or further ECT (although the latter is not recommended by some authorities ) but remains high. Common initial adverse effects from ECT include short and long-term memory loss, disorientation and headache. Although objective psychological testing shows anterograde memory has mostly returned to baseline by one month post treatment, ECT remains a controversial treatment, and debate on the extent of cognitive effects and safety continues.

Depression - Herbal remedies
Two products, St John's wort and S-Adenosyl methionine, are available as prescription antidepressants in several European countries, and are classified as herbal supplements and sold over-the-counter in the UK and US. There is inconsistent evidence on the effect of St John's wort extract on major depression. The pharmaceutical quality of the extract has an effect on the safety and efficacy for the treatment of any type of depression, and the quantity of active ingredient varies between different preparations. St John's wort interacts with a number of prescribed medicines including other antidepressants, oestrogens and progesterones, and can reduce the effectiveness of oral contraceptive pills.

Clinical trials of S-Adenosyl methionine have shown that it is equivalent to tricyclic antidepressants in effectiveness, although the safety and efficacy of over-the-counter versions is unknown. Other supplements such as omega-3 fatty acids, tryptophan, and 5-hydroxytryptophan, have shown no effect beyond those of placebo.

==Repetitive transcranial magnetic stimulation Repetitive transcranial magnetic stimulation utilizes powerful magnetic fields which applied to the brain from outside the head. Multiple controlled studies support the use of this method in treatment-resistant depression; it has been approved for this indication in Europe, Canada, Australia, and the US. It was inferior to ECT in a side-by-side randomized trial.

==Phototherapy Bright light therapy, a form of phototherapy has been found to be an effective treatment for the winter depression produced by seasonal affective disorder. There has been some conflicting evidence as to its effectiveness for non-seasonal depression. Physical exercise has been proposed as an alternative form of treatment, and is recommended by U.K. health authorities, but systematic review has not been conclusive on its effectiveness in symptom reduction. Vagus nerve stimulation was approved by the FDA in the United States in 2005 for use in treatment-resistant depression, although it failed to show short-term benefit in the only large double-blind trial when used as an adjunct on treatment-resistant patients.

Depression - Diets
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