Try ~1 g of EPA+DHA/day (i.e., 2 capsules of OmegaRx per day taken during a meal). Upward titration to ~2 g/d after 1-2 months as indicated based on efficacy and tolerability.  Hope this helps!

Depends on what the patient on at the time of relapse. Options generally include adding another antidepressant (such as Mirtazapine to SSRIs/ SNRIs), switching to a different antidepressant (e.g. Venlafaxine, duloxetine, TCA) or augmenting with Lithium. Further options are also available though you should perhaps try one of these first. Best wishes

Thank you, all options that you cited are valuable. However, my question was more general and I though about old guidelines which suggested to reduce the dose to half dose in the manitanance phase. According to these guidelines, if patients experienced a new episode, an increasing of dose should be the first choice and often this strategy was effective. Nowadays, with manitenance thearpy a full dosage, in the case of new depressive episode we have to move to augmentation, combination etc, as you cited. The current strategy was supported by several evidences which reported that it allow to reduce the frequencies of depressive episode. However, these evidences came manly form studies with a maximum of 5 years or, rarely, 10 years of follow-up. Thus, my question is: in the very long-term (i.e. in the lifespam) the current strategy is realy the best for the patients?

... and psychotherapy? The S1-guidelines for depression prefer a combination of pharmaco- and psychotherappy, will mean, that's - perhaps - not only a question of pharmacological strategy

Yes, of course. I also think that the combination between pharmaco and psychotherapy could be considered the best treatment for depression, but in our country due to economical reasons, it is not simple to be offered to all patients. Therefore, often pharmacotherapy is the only options for many patients.  

We and others have found that fish oil (a rich sorce of EPA+DHA) supplementation augments SSRI efficacy in adolescent MDD patients (i.e., PharmaNutrition. 2014;2:38-46). The benign side effect profile is a plus and likely also corrects underlying LCn-3 deficiency. Adjunctive treatment with other anti-inflammatory drugs (e.g., ibuprofen) is also an option. This is not a 'conventional approach' but is supported by a growing body of research implicating elevated immune-inflammatory signaling in the pathophysiology of depression.

The options are : switching to another antidepressant / counselling (socio/psycho/spiritual methods).Hope this will help.

Rudiger had a great response. There is little empirical evidence regarding a treatment strategy, whether pharmacological or psychotherapeutic, for the long term. However, some studies comparing medications to psychotherapy show that the change of psychotherapy may be more profound across time.

Empirically, psychotherapy is at least as effective as medications, especially in light of revelations such as the Turner 2008 NEJM article noting low efficacy of unpublished but registered antidepressant trials.

If antidepressants do not seem to be working well for depression, it might be wise to work strongly to get the person connected with psychotherapy. Yes, resources are limited in most places. People can benefit to some degree from support groups including online, and can benefit from self-help with recognized self-help resources.

Telemedicine is now blossoming. This can overcome geographic barriers to care. As healthcare professionals, we can help clients review and select therapists, self-help groups, and self-help books/manuals.

Physician prescribers can get trained in the basics of talk therapy through resources such as "The Fifteen Minute Hour." Ideally, by most professional standards guidelines, when venturing into a new area of practice, the physician should set up some kind of supervisory relationship with someone who is well-skilled in the intervention.

At least, the client should be made aware that psychotherapy is a legitimate, well-advised treatment course, even if not readily available.

Paul, thanks alot for your vote. In Germany psychotherapy is well established, health insurances pay about 1,5 Billion € for outpatient psychotherapy, but about 3 Billion für Psychopharamcotherapy and about 4,5 Billion for inpatient psychiatry, inside there's only a very smaller piece psychotherapy. On the other Hand, psychotherapy is not only effective for the most patients but also for the society:  return on investment (ROI) was estimated between 1:3 and 1:4,5, means that society get the investment back. To change the situation for patients, is certainly a lengthy and foremost a political process, but the arguments for psychotherapy are very good. For more information see my paper: https://www.researchgate.net/publication/269572241_Versorgung_psychisch_kranker_Erwachsener_in_Deutschland_-_Bedarf_und_Inanspruchnahme_sowie_Effektivitt_und_Effizienz_von_Psychotherapie

best, Rüdiger

Article Versorgung psychisch kranker Erwachsener in Deutschland - Be...

Rudiger: thanks for noting your article. I do research concerning policy influences and professional practice influences upon access to mental health care. Would there be a way for one of your team to translate the article into English? I can get that done on my side, but it might come out more true to the original if done by an author rather than a reader. This would take time, so if possible no hurry.

Paul, i'll try to get someone for translation, best Rüdiger

Dear Stefano, nice to meet you here and greetings to Italy. My first idea is to detect possible fakers of depression which worsen or prolong depression.

These are 1. a lack of vitamin D3,  2. a deficit in zinc (low BDNF) and 3. a possible high homocysteine level (methylfolate +-B-12). which is attacking the blood-brain barrier (continuous low level poisining)..

Increasing BDNF in my opinion is a good idea which can be done by physical activity (walking, jogging, treadmill) and fishoil. A blood test on DHEA could be helpful explaining the low quality of sleep if sleep is not refreshing.

Fishoil is also helpful especially if patient is avoiding saturated fats from red meat for a limited time. Saturated fats from heated red meat is counteracting unsaturated fats and may cause insulin resistance in the brain. The kick in time is

around 4 weeks if used as a stand alone med but can be reduced to a week if fishoil (aka 1,5 gram EPA) is combined with 100 grams (fresh milled) almonds daily.

My second idea goes to inflammation markers.

In depression interleukine-1 beta, interleukine-6, TNF alpha are elevated.

A simple solution without side effects are 25 gram blueberries daily which

are reducing IL-1 beta. But there are much more solutions available , for example

resveratrol. If your patient is overweighted some attention is

needed to reduce the elevated C-reactive Protein level in addition which can be

done by fruits several times a day fiven to meal. I consider massive belly fat as  an

endocrine system which cannot be neglected. On the other  hand antidepressants which cause a massive weight gain are not helpful if you look at inflammation markers.

Dear Stefano,

This is very interesting question and it is hard to answer on this question, which sounds very easy. Why? I have some ideas:

- we do not have many studies with polypharmacy (long term studies). It is known that adverse effects (events) are more frequent with number of drugs taken and their combinations.

- we have a small amount of studies where are compared switching strategy or 'add on'. Usually the trials are small and short term. According to the last trials 'add on' strategy is better than switching, but polypharmacy is highly underestimated. I do not recommend combination of SSRI+TCA or even TCA+new drug (especially in old patients).

- If We take results from STAR-D trials the outcomes are better (% patients in remission) If We use polypharmacy than switching.

- We have few trials where combination is compared with monotherapy (e. g. mirtazapine and venlafaxine) and We have few negative reports in Medline (e. g. bupropion and duloxetine compared to monotherapy)

If I conclude, We do not have the long-term trials and therefore a clear conclusion cannot be made. If there is first episode, there is better to wait until the end (1 year). If it is second or third episode of MDD there is better to switch, because a long term use is usually not avoidable.

Next to these statements there are also some extra options (e. g. use of ibuprofen or Celecoxib) as add on strategy, however negative impact on adverse events occurrence should be calculated (look at inflammation markers).

Important question is also pharmacokinetics of antidepressants, because maybe patients used some extra drugs (e. g. amlodipine, rifampicin), which can produce a lack or extra effects (usually adverse events) and therefore a cooperation between psychiatrist and clinical pharmacist/pharmacologist is very important. Also You should calculate non-adherence and try to find the reason for it. Sometimes We add extra drug and We do not calculate for non-adherence. In addition, I should add the changes in clearance and liver status, which can have a serious impact on final effects.

Maybe patients have also another 'new' diseases (e. g. psoriatic arthritis), which can induce a lower lewel of folic acid and therefore problems in synthesis of monoamines. Also some drugs can lower production of monoamines (e. g. methotrexate, leflunomide).

As a clinical pharmacist specialist I often deal with these problems, where these problems are very important and with cooperation we usually get better clinical outcomes for our patients (e. g. complete remission).

Regards,

Mathew