How is depression treated today?

The increasing number of depression patients has been extensively discussed since the pandemic; is this the effect of COVID-19 related isolation?

This is difficult to determine. We have diverging data. Some research projects demonstrate that in terms of psychiatry, the pandemic has actually not had such horrific consequences as were anticipated. Obviously, the number of depression cases is growing slowly. But it is more strongly related to the increasing awareness of the disease. More and more people are aware of what the disease is, and they make an appointment with a doctor when they notice its symptoms.

What are the indicative signs of the disease?

The first of these is a feeling of misery, commonly recognized as sadness. Yet sadness does not always mean depression. Nor does a ‘bad day’, or a seasonal bad mood in the fall.

We are bound by the ICD 10 classification. It lists the diagnostic criteria for depression. To be diagnosed with depression, the patient has to feel depressed (sad) for at least two weeks, most of the time each day. Among other symptoms, they are unable to experience pleasure (anhedonia), they lack motivation, experience sleep disorders, withdrawal, they find it hard to focus or to engage in any activity. 

So if someone is focused on their sadness, they are unable to feel happy about anything, and these symptoms persist for a prolonged period of time, this person should see a doctor. Particularly when their condition affects their daily functioning - they are reluctant to leave their home, to meet friends or family, they go on a medical leave.

What other symptoms may conceal depression?

Somatic masks of depression are purely physical symptoms, typically headaches, gastrointestinal issues or sleeplessness. These are prolonged and resistant to treatment. The patient is pushed from one specialist to another. None of the doctors is able to give the right diagnosis while the symptoms persist.

Which doctor should see a patient with symptoms of depression? 

The patient can go to a primary care physician. As the Polish Society of Psychiatry, in collaboration with the Polish Chamber of Physicians and Dentists (NIL), we have written a set of guidelines for primary care physicians on the treatment of depression. These are available at the NIL website. Thus, family doctors are capable of diagnosing and treating depression, and they may refer the patient to a psychiatrist in more complicated cases. 

Anyway patients may feel more comfortable seeing a family doctor instead of going to a shrink right away - using psychiatric help is still stigmatizing in Poland, and psychiatrists are treated as the last resort.

What is more effective as treatment: psychotherapy or medication?

Preferably, both should be used. But in reality, you have to wait for group therapy funded by the Polish National Health Fund (NFZ) for a few months, and even longer for individual therapy. Doctor appointments are more accessible and as a result, we usually start with pharmacotherapy. Some patients feel so bad that they would even be unable to take part in therapy regularly. They need to be pulled out of this state. We usually use the traditional SSRIs - selective serotonin reuptake inhibitors. But to see the effects of these drugs, you also have to wait 2 to 4 or even 6 weeks of using the product at the right dosage.

Do patients with depression need hospital treatment?

Today, depression is treated mainly on an outpatient basis. Hospital treatment is needed in cases of strong suicidal thoughts or attempted suicide evaluated as serious. It is also true for cases involving psychotic symptoms (hallucinations). 

Recently, the media reported that the most popular SSRI drugs are not effective in treating depression. Is this true?

We first started administering SSRIs in the 1990s. Before they were introduced, they had to undergo clinical trials in which they were proven effective in comparison to a placebo. 

The media fuss was initiated by a publication by Joanna Moncrieff and her collaborators. The article was published in Molecular Psychiatry. Moncrieff’s analysis attempted to demonstrate that depression does not involve lowered serotonin levels. 

The researcher checked several markers, such as the level of serotonin metabolites in cerebrospinal fluid, she was also reviewing imaging results and genetic tests. These reviews showed there was no evidence of lowered serotonin levels in depression. 

This research was criticized by other researchers. There were allegation of inadequate choice of tests. For example, a lot of PET neuroimaging of serotonin receptors and their functioning would not be included by Moncrieff in her analysis. 
We should further emphasize that the theory of serotonin in depression has never been a yes/no matter. We have long been aware that depression does not rely on serotonin deficiency only. We are dealing with a much more complicated and multifaceted disorder. Therefore, it is not right to assume that a patient with a low serotonin level, which we will increase by administering SSRIs, will be cured as a result. This is not so simple. We should bear in mind that there are several theories of depression, such as the theory of inflammatory depression. We have multiple mechanisms affecting depression. 
Now about the SSRIs. Moncrieff actually only wrote one single sentence about them. In her opinion, they are numbing to our responses and our emotionality. So it is not true that these drugs do not work. They do, and this is confirmed by patients.

I recently asked my physician colleagues whether they have had cases of patients refusing to take SSRIs because they read on the Internet that these do not work. Nobody had such patients. Depressed people take their medication because it makes them feel better, and there is scientific evidence of their effectiveness, which is consistent.

When can you be certain that you are dealing with treatment-resistant depression?

Treatment-resistant depression affects approximately 30% of all patients, which is a relatively high percentage. According to the recommendations of the Polish Society of Psychiatry, published in Psychiatria Polska, you have to wait up to 8 weeks from the commencement of use of the medication in order to diagnose a treatment-resistant depression. In practice, when there is no improvement after 4 weeks, we can increase the dosage and wait 4 more weeks. After that, the treatment model should be changed.

What options do you have in such cases?

Different strategies are available. The doctor can switch to a different drug, use a combination of drugs, or electroconvulsive therapy. The latter works very well in severe cases of depression with psychosis. Many patients are skeptical about electroconvulsive therapy. Their opinions are based on movies such as One Flew Over the Cuckoo’s Nest. In fact, this is a very safe procedure today. It is done under short-term anesthesia, in the presence of an anesthesiologist, with EEG monitoring. Yet it is not offered by many hospitals. Moreover, there are a lot of contraindications for ECT. 

Recently, we have been given the option of applying esketamine treatment in treatment-resistant depression. This type of therapy is refunded under a drug program. It involves quite severe restrictions. Patients are only eligible to qualify for the program if they meet very strict criteria. Treatment is available to adults (aged 18 to 75) with treatment-resistant depression, having a subsequent episode of the disease (not earlier than during a second episode). The episode has to last at least six months and must be documented. At least two treatment attempts must have been completed, involving not more than 5 changes of medication. Esketamine treatment is not allowed in cases such as bipolar depression, existing and past addictions, and personality disorders such as borderline personality. 

What is esketamine and how is it administered?

Esketamine is a variant of ketamine, which is an anesthetic with a narcotic effect. In esketamine, this narcotic effect is strongly reduced. 

Intranasal product is administered in treatment-resistant depression, outside of hospital. Treatment is refunded for 8 months. In the first phase, which is the first month, esketamine is administered twice a week. Later, it is given on a weekly or biweekly basis.

It should be emphasized that esketamine is an added treatment, meaning that the patient continues to take a conventional antidepressant (SSRI or SNRI).

How long does it take for the patient to feel the effects of such treatment?

The patient’s mental state improves immediately, which is what makes esketamine different from other drugs used in depression. However, this effect is often transient. This type of therapy certainly requires further observation, for example to determine the duration of improvement without maintenance treatment. 

We should note that many patients treat esketamine as a wonder drug, while in fact this medication is not 100% effective. There are patients who will not respond to esketamine. 

Can we call esketamine treatment as a breakthrough in treatment of depression?

Certainly it is different from SSRIs or SNRIs. Esketamine has a different mechanism and yields an immediate effect.
New methods of depression treatment are being actively sought nowadays. Research is pending, for example, on the antidepressant properties of psilocybin (magic mushrooms) and other psychostimulants, which also affect serotonin transmission. These drugs were first used as psychoactive substances. 

Is esketamine itself a breakthrough? We have not had too many breakthroughs in psychiatry. The 1950s saw the emergence of neuroleptics, or antipsychotics. Then, tricyclic antidepressants (TCAs) were introduced. These were used by the end of the 1990s when SSRIs and SNRIs first appeared, which was a revolution. Now we have the esketamine treatment. This is a change. But it will still take us years to assess the effectiveness of this treatment in real-life conditions.

Interviewed by Iwona Kołakowska
Fot. Michał Teperek
Communication and Promotion Office