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April 2017
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Scientific research indicates that a high percentage of people who suffer from depression (about 70%) respond positively to pharmaceutical treatment when the medicine is prescribed in correct doses and for the right length of time. If there is not a satisfactory response to the first attempt of antidepressant treatment, it may be that a different antidepressant should be prescribed. To date, although there is no antidepressant medication which is more effective than another, in absolute terms, it is common to see that each individual has his/her specific way to respond and therefore it is not possible to determine, in advance, which antidepressant will be effective for which person. In addition to the drug, there are other treatments available, such as psychotherapy, psychiatric drug therapy integrated with psychotherapy, therapy and electroconvulsive therapy and white light therapy. Each of these approaches has specific prescriptions, for example, drug treatment or drug therapy integrated with psychotherapy have success rates ranging from 60-80%. The integrated method has its own particular requirements, in the form of protracted depression, which concerns the persistence of symptoms left over between episodes, and in other forms in which drugs or psychotherapy alone have not proven effective.

Pharmacological therapy

This type of therapy is becoming ever more central to the treatment of depression and this has meant that professionals are now considering other types of treatment, even if effective, to be used as an integration rather than a substitute for drugs.

Treatment for depression is carried out in four different stages, or phases:

  • acute phases 1 and 2 (priority emergency treatments and treatments for curing the episode);
  • protracted stages 3 and 4 (consolidating treatments of symptomatic remission and/or prevention of relapsing and relapse prevention treatments).

The first two phases are aimed at first controlling and then eliminating not only risky behaviour but also depressive symptoms, and allow the patient to return to a state of wellness. Phases 3 and 4 are aimed at preventing relapses, or rather a reactivation of the symptoms and they usually last for 4-6 months. After phase 4, or the long-term treatment, and especially in recurring forms of depression (3 or more episodes), a maintenance type of therapy is implemented, aimed at preventing the onset of a new depressive episode. The World Health Organisation recommends a maintenance therapy for 6-9 months after the disappearance of depressive symptoms if the person has had three depressive episodes, with at least two being within the last 5 years. With this strategy, risks of relapsing have reduced by 50%. 

There are different types of antidepressant medications currently available which can be used to treat depression. Each of these classes of drugs works in a different way. In short, these drugs facilitate an increase in neurotransmitters (serotonin, norepinephrine, dopamine) in the synapses and, consequently, receptors are stimulated in this way too. Thus, these drugs correct altered biochemical mechanisms. However, their mechanism of action not only enhances the neurotransmitters involved in the disease (desired effect), but also causes some negative actions (side effects), but these are temporary, transient and dose-dependent. They are effective drugs in any case and they must be chosen in a specific way and taken regularly according to specific rules and for a sufficient length of time. The result of the medicine is evident after variable periods, ranging from 3-4 weeks, but some may need more time to reach maximum effectiveness. Although all drugs are potentially effective, the response to each molecule is very individual. The decision about which type of medication to choose depends on the type of depression, the characteristics of the person and the side effect profile of the drug.

Depending on the different results and the systems which regulate nerve transmission, medicine can be categorised as follows:

Classic antidepressants

Non-selective reuptake inhibitors (Tricyclic: Amitriptyline, Desipramine, Nortriptyline, Doxepin)

These are drugs which have been on the market for many years and which, in invariable and unspecific ways, inhibit the reuptake of norepinephrine and serotonin. They are effective drugs, however they can cause sedative and cardiovascular side effects. There are not recommended for patients with glaucoma, prostatic hypertrophy or heart disorders or the elderly in general.

Irreversible monoamine oxidase inhibitors (MAOIs: Phenelzine, Tranylcypromine)

These can cause hyptension and using them requires special dietary restrictions and attention must be paid to pharmaceutical interaction.

Reversible inhibitor of monoamine oxidase (RIMA: Moclobemide, Toloxaton)

These are free from the side effects of MAOIs and they do not require any dietary restrictions.

New generation antidepressants

Selective serotonin reuptake inhibitor (SSRI: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram)

These drugs are selective against serotonin, inhibiting the reuptake of this neurotransmitter and, as well as being equally effective as classic antidepressants, they have a much higher safety profile and tolerability. These drugs can be used by patients with cardiovascular problems and other organ diseases. They are also recommended for the elderly. Side effects include transient nausea and an upset stomach.

Serotonin and norepinephrine reuptake inhibitor (SNRI: venlafaxine, milnacipran)

These inhibit the reuptake of both serotonin and norepinephrine. They are equally as efficient as classic antidepressants, but with greatly reduced side effects.

Norepinephrine reuptake inhibitor (NARIs: Reboxetine)

These work by inhibiting the reuptake of norepinephrine, showing good efficiency and reduced side effects, mainly relating to insomnia and pressure.

Antidepressants of atypical mechanisms

Mianserin, maprotiline, amineptine, sulpiride, Levosulpiride, S-adenosyl-methionine, trazodone, mirtazapine

These substances act on receptors and not on reuptake, involving both the dopaminergic pathways and the serotonergic-noradrenergic pathways. These molecules are very different for each other in terms of the mechanism of action and their side effects. However, they are still effective and have temporary and limited side effects. S-adenosyl-methionine has a good safety and tolerance profile. .

Other pharmaceutical treatments

In some cases of depression, particularly in recurring depression or bipolar depression, so-called mood stabilisers can be used, such as lithium salts, valproic acid and carbamazepine.


The use of benzodiazepine (anxiolytics, which induce sleep) in combination with antidepressant therapy can be helpful in some cases, such as in the early stages of antidepressant therapy, in patients with high levels of anxiety, tension and restlessness and insomnia. Their use must be temporary and monitored by a doctor since they can induce consumption habits and sometimes even abuse.

Side effects
Some of the most common side effects of antidepressants are: dry mouth, blurred vision, constipation, dizziness, drowsiness, changes in body weight, insomnia, restlessness and headaches. Particular attention must be paid to problems relating to urinary, sexual and cardiovascular functions. These effects can be more intense and serious in the elderly: use by these patients must be justified and well monitored. The most common side effects of SSRIs and SNRIs include nausea, decreased appetite, tremors and sleep disturbances. Effects are usually temporary and only occur in 10-15% of patients treated. They do not require special diets, nor do they induce weight gain, and there are no particular interactions with other drugs. They are safe for elderly patients or those with organ diseases. In conclusion, the benefit-risk profile of the SSRIs and SNRIs are often better than traditional tricyclic antidepressants since there are fewer side effects, better tolerability and they result in greater adherence to treatment. None of these antidepressants induce addiction. Their use, even for long periods, is safe in this respect, and, in general (at least for new generation ones), their toxicity is very low.

Important rules to know when taking medication and managing side effects
Antidepressants are effective and safe drugs but only an experienced doctor can decide which drug to prescribe following diagnosis.

  • Medicine must be taken according to the specific indications regarding the dose and the length of the assumption.
  • Therapy must not be suspended or changed without prior consultation.
  • Medication taken for other treatments must be reported to avoid any possible interaction. Any annoyances experienced during therapy must be communicated. When experiencing a dry mouth, drink a lot of water, suck on sugar free sweets and take extra care of your dental hygiene.
  • Eat lots of fruit, vegetables and fish. If constipated, consume fibre and liquids and try to avoid using laxatives. To work against the effects of pressure, do physical activity outdoors.
  • Keep medicine in a cool, dry place and not in the bathroom as humidity can degrade it. Keep medicine out of the reach of children.
  • If you notice that you have missed a dose which you should have take 6-8 hours ago, take the next dose but do not take the missed dose.
  • Limit consumption of tea, coffee and drinks containing caffeine and reduce or completely stop drinking alcohol. Inform your other medics (the dentist, anaesthetist) that you are taking antidepressants. It is not common to interrupt a course of antidepressant but, if so, it only lasts a few days. Oral contraceptives can still be taken with antidepressants.

Pregnancy and breastfeeding

It is uncommon for women to become depressed during pregnancy, however, it is common for women to get depressed after pregnancy and whilst breastfeeding. If a woman shows signs of depression during the first trimester, it is best to avoid medication. If depression occurs during the second or third trimester however, this treatment course can be considered, but only by a specialist. When breastfeeding, 30-70% of women show signs of ‘maternity blues’ and 10-20% suffer from depression. Maternity blues often occurs the week after giving birth and usually goes away 7-10 days after it appears. If it does not go away though, and turns into depression, breastfeeding must be stopped so the mother can take antidepressants. If a woman wishes to get pregnant whilst taking antidepressants, she will need to discuss this with her doctor to agree on how and for how long she can stay off the antidepressants.

Patients with cardiac illnesses

Tricyclic antidepressants should be avoided for people with cardiac rhythm problems or who have suffered from ischemic, heart attack or angina pectoris problems, because these drugs act on the heart’s rhythm, complicating the aforementioned problems. New generation antidepressants are better in these cases (SSRIs or SNRIs) as they are risk-free if taken correctly and can help cardiac problems. The same goes for arterial hypertension problems or heart failure as tricyclic and IMAOs are not recommended in these cases.


Tricyclic antidepressants must be avoided in cases of glaucoma because they can aggravate eye conditions.

Prostatic hypertrophy

The same goes for people suffering from prostatic hypertrophy, which can go as far as acute retention of urine.

Medication and sexual activity

In some people, antidepressant drugs can cause difficulties in the sexual sphere, especially regarding a reduction of desire, which is similar to what already happens as a result of depression itself, and difficulty in reaching orgasm and ejaculation. These effects are often temporary and disappear after discontinuation of treatment. However, it is best if the patient talks openly about this with the specialist to evaluate the possible use of antagonist medication or a decrease or change in the dose of medication.

Elderly depressed patients
13-15% of elderly people are depressed. It often occurs together with organ diseases and this may be influenced by the course of depression. The elderly are sometimes treated with more drugs than younger people, which is why it is particularly important to consider both the modified metabolic capacities and pharmaceutical interactions with other molecules, especially steroids, antiarrhythmics, anticoagulants and anti-asthmatics drugs. For this reason it is advisable to use SSRIs or SNRIs rather than tricyclic antidepressants. In addition, the latter can also (because of what they do) cause attention, concentration and memory disturbances and there may be further deterioration of performance, functional and social skills and, ultimately, they might jeopardise the patient's quality of life. On the contrary, the use of SSRIs or SNRIs seems to play a positive role in cognitive functions.

There are different approaches for psychological treatment of depression: cognitive and behavioural, interpersonal, psychodynamic, phenomenological treatment, and so on. Recent studies indicate a success rate of 30-35% for psychotherapy alone, and it is particularly suitable for mild to moderate cases, for which the success rate seems even higher. In severe forms, on the other hand, pharmacological treatment remains the basic treatment, but patients do benefit from a psychological approach as a means of support.

In a general sense, psychotherapy modifies erratic thoughts, ideas and attitudes (behaviour), supports and helps the patient in a continual way and improves interpersonal relationships and self-esteem. Psychotherapy is particularly good for patients with reactive or situational depression, that is, depression triggered by specific events and limited over time (for example, depression caused by stress, a death and conflicts). Psychotherapy is not considered an alternative to pharmaceutical therapy and, no matter what the approach, is must always be recommended by a psychiatric specialist.


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