Depression and Medication
Dr Jonathan Haverkampf
Depression should be treated with a combination of psychotherapy and medication if it is serious enough. In less severe cases, especially when it is a reaction to obvious external factors, psychotherapy alone may do. Medication can especially provide relief before the effect of psychotherapy, which is more geared towards the long-run, takes hold. While medication cannot make life more meaningful per se, it can reduce the low feelings, the loss of interest in activities and improve one’s sleep, for example.
Suicidality needs to be kept in mind in any form of depression and the mainstream opinion has shifted towards addressing them rather than maintaining silence about suicidal thoughts in the fear that merely asking about them one might trigger them. A concern was that since the activating effect in several antidepressants normally occurs before the antidepressant affect, the risk for suicide might increase because a patient who still feels depressed becomes more active. However, the clinical experience is that having something that can potentially help against the depression, reduces the pressure towards self-harm a patient may feel. As I have outlined in another article on depression, facilitating the idea of a future the patient has some control over is often an important step in treating depression.
The selective serotonin reuptake inhibitors (SSRI) are the most common used antidepressants because of their relative safety and low side-effect profile. Unfortunately, in the beginning the indiscriminate use of the SSRI Prozac® against ‘everything’ from workplace problems to the stress of unhealthy living lead to a backlash in the media, which unfortunately made many patients avoid all medication out of fear to become emotionally flat or experience a change in one’s personality, which has not been shown so far in any convincing way.
There are several other substances, that work as antidepressants, and all have potential side-effects. Often a substance is used which has a ‘desirable’ side-effect and that deals more effectively with the individual constellation of symptoms:
- Insomnia: Mirtazapine (Remeron® and many generics) is effective in inducing sleep at lower doses (around 15mg), an effect that seems to wear off once one goes up to 45mg. However, the antidepressant effect of 15mg is usually too small. Especially early on ‘hangovers’ in the morning are not uncommon. Among very common side effects are dry mouth, constipation, increased appetite, as well as somnolence, sedation, sleepiness (which may wear off).
- Lack of activation: Venlafaxine (Effexor®, Effexor XR®, Lanvexin®, Viepax®, Trevilor®) is a noradrenaline and serotonin reuptake inhibitor (NSRI) and often affectively increases activation. However, one should be careful with patients who might harm themselves (or others) because activation often occurs before the antidepressant effect takes hold. Also, if used in cases of anxiety it may increase the anxiety before reducing it.
- Co-morbidity with anxiety, panic attacks, OCD: the SSRIs are a good first choice. Venlafaxine seems to be helpful with anxiety, but often it increases anxiety early on, and possibly even medium-term.
Tricyclic antidepressants should not be used to treat symptoms that can be treated with the SSRIs or an NSRI, because of the letter’s better safety profile. It is difficult to imagine there still is an application for MAO inhibitors, except in the rare depression that does not respond to treatment. In the latter cases, my experience is that often medication has not been administered long enough or prescribed in the right dose. Quite frequently there has been no or only inadequate psychotherapy. It is worth remembering that psychotherapy is still and will always be the core treatment for what were a century ago referred to the ‘neurotic’ conditions, such as reactive depression, anxiety, OCD and the like. The reason is that the symptomatology can be traced to problems in interactions, communication and human relationships. Generally, there is better empirical evidence for the usefulness of antidepressants in the treatment of depression that is chronic (dysthymia) or severe.
In any case, it can take weeks for the full effect of medication to be noticed. A 2008 review of randomized controlled trials concluded that symptomatic improvement with SSRIs was greatest by the end of the first week of use, but that some improvement continued for at least 6 weeks.
Major depressive disorder
The UK National Institute for Health and Care Excellence (NICE) 2009 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression, because the risk-benefit ratio is poor. The guidelines recommend that antidepressant treatment should be considered for:
- People with a history of moderate or severe depression,
- Those with mild depression that has been present for a long period,
- As a second-line treatment for mild depression that persists after other interventions,
- As a first-line treatment for moderate or severe depression.
The guidelines further note that antidepressant treatment should be used in combination with psychosocial interventions in most cases, should be continued for at least 6 months to reduce the risk of relapse, and that SSRIs are typically better tolerated than other antidepressants.
Non-Responders
Between 30% and 50% of individuals treated with a given antidepressant do not show a response. In clinical studies, approximately one-third of patients achieve a full remission, one-third experience a response and one-third are non-responders. Partial remission is characterized by the presence of poorly defined residual symptoms. These symptoms typically include depressed mood, psychic anxiety, sleep disturbance, fatigue and diminished interest or pleasure. It is currently unclear which factors predict partial remission. However, residual symptoms are powerful predictors of relapse, with relapse rates 3–6 times higher in patients with residual symptoms than in those who experience full remission.
“Trial and error” switching
The American Psychiatric Association 2000 Practice Guideline advises that where no response is achieved following six to eight weeks of treatment with an antidepressant, to switch to an antidepressant in the same class, then to a different class of antidepressant. A 2006 meta-analysis review found wide variation in the findings of prior studies; for patients who had failed to respond to an SSRI antidepressant, between 12% and 86% showed a response to a new drug. However, the more antidepressants an individual had already tried, the less likely they were to benefit from a new antidepressant trial. A later meta-analysis found no difference between switching to a new drug and staying on the old medication; although 34% of treatment resistant patients responded when switched to the new drug, 40% responded without being switched.
Combination
A combination strategy involves adding another antidepressant, usually from a different class to have effect on other mechanisms. Although this may be used in clinical practice, there is little evidence for the relative efficacy or adverse effects of this strategy.
Augmentation
For a partial response, the American Psychiatric Association guidelines suggest augmentation, or adding a drug from a different class. These include lithium and thyroid augmentation, dopamine agonists, sex steroids, NRIs, glucocorticoid-specific agents, or the newer anticonvulsants.
US prescriptions in 2010
| Drug name | Commercial name | Drug class | Total prescriptions |
| Sertraline | Zoloft® | SSRI | 33,409,838 |
| Citalopram | Celexa® | SSRI | 27,993,635 |
| Fluoxetine | Prozac® | SSRI | 24,473,994 |
| Escitalopram | Lexapro® | SSRI | 23,000,456 |
| Trazodone | Desyrel® | SARI | 18,786,495 |
| Venlafaxine (all formulations) | Effexor (IR, ER, XR) ® | SNRI | 16,110,606 |
| Bupropion (all formulations) | Wellbutrin (IR, ER, SR, XL) ® | NDRI | 15,792,653 |
| Duloxetine | Cymbalta® | SNRI | 14,591,949 |
| Paroxetine | Paxil® | SSRI | 12,979,366 |
| Amitriptyline | Elavil® | TCA | 12,611,254 |
| Venlafaxine XR | Effexor XR® | SNRI | 7,603,949 |
| Bupropion XL | Wellbutrin XL® | NDRI | 7,317,814 |
| Mirtazapine | Remeron® | TeCA | 6,308,288 |
| Venlafaxine ER | Effexor XR® | SNRI | 5,526,132 |
| Bupropion SR | Wellbutrin SR® | NDRI | 4,588,996 |
| Desvenlafaxine | Pristiq® | SNRI | 3,412,354 |
| Nortriptyline | Sensoval® | TCA | 3,210,476 |
| Bupropion ER | Wellbutrin XL® | NDRI | 3,132,327 |
| Venlafaxine | Effexor | SNRI | 2,980,525 |
| Bupropion | Wellbutrin IR | NDRI | 753,516 |
In any case, medication should always be combined with psychotherapy. Especially in the less severe forms of depression and those that seem to have an explanation and are “reactive” medication may be less helpful and psychotherapy eventually leads in many cases to a full remission of symptoms.
© Dr Christian Jonathan Haverkampf. All rights reserved.
Psychotherapy & Counselling, Communication, Medicine (Psychiatry); Dublin, Ireland
www.jonathanhaverkampf.com, www.jonathanhaverkampf.ie
This article is solely a basis for academic discussion and no medical advice can be given in this article, nor should anything herein be construed as advice. Always consult a professional if you believe you might suffer from a physical or mental health condition.
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