The Krka Talks podcasts are aimed to promote and share knowledge and experiences of healthcare professionals gained from years of dedicated practice and clinical work. The discussions are therefore intended for healthcare professionals who wish to learn from established specialists as well as individuals keen on exploring contemporary approaches to health and wellness.

Talks are based on speakers’ expertise and intended for HCPs around the world with the goal of having a positive impact on patient care.

The chemistry behind depression: Symptom-specific treatment

In this episode, we discuss specific symptoms of depression that are associated with an increase or decrease of specific neurotransmitters – dopamine, serotonin and noradrenaline. Knowing which particular neurotransmitter is associated with which particular symptoms of depression may help doctors choose the right medicine and provide the best chance of treatment response.

Piotr Wierzbiński MD, PhD, Poland

Piotr Wierzbiński holds a private medical practice in Lodz, Poland. As part of his research development he participated in internship at the Department of Mental Health, University of Siena School of Medicine, Italy. He is the author of over 80 medical publications including those involving panels on epidemiology and pharmacotherapy in psychiatry, sports psychiatry, suicide, and on the overlapping fields of somatic medicine and psychiatry.

Assoc. Prof. Ante Silić, MD, PhD, Croatia

Ante Silić is Associate Professor at the School of Medicine at the Catholic University of Croatia. He is subspecialized in social and biological psychiatry and works at University Hospital Centre Sestre Milosrdnice, Zagreb. He is focused on psychiatric research and everyday clinical practice.

Piotr Wierzbiński: Depression has many faces. Can you imagine that somatic pain, lack of energy, and easy fatigue can be the main symptoms of depression?

Ante Silić: Welcome to Krka talks. I have the honour to present here today my dear colleague Piotr Wierzbinski. My name is Ante Silić. I’m a psychiatrist from Zagreb. I work at University Hospital Sestre Milosrdnice, and today my colleague and I will be talking about depression. It’s a huge subject. Where do we start?

Piotr Wierzbiński: We start by saying that everyone of us has a patient with depression, and this is a serious epidemiological problem, especially after COVID and because of life. We have different lives now than twenty years ago, forty years ago. People live in a different way. We have overstimulation from many factors, and people try to change something. The first step to depression is diet and lack of sleep, and the next step is low mood, lack of energy. We have many patients with anergia and ‘battery off’.

Ante Silić: One of the things that we hear these days is – I mean the World Health Organization has been saying that to us, all of us – that depression is moving forward in numbers. And it actually did so. It went from the fifth place to the second place, now it’s at the first place. And then we can hear some criticism about it, that we are doing the inflation, that we are modifying the diagnostic criteria in the era of transition from DSM-4 to DSM-5 or ICD-11 and so on and so forth. So basically, is there really more depression these days or is it something artificial? What’s your opinion on that?

Piotr Wierzbiński: My opinion is simple. I have many patients in my practice, and people suffer from depression because of biology, because of lifestyle, because of stress. We should change the point of view for depression. Because many depressions now are a comorbidity with anxiety, and we have many factors that are important in that aetiology, like hypercortisolaemia, stressful life events, and many of us don’t sleep well, and we have no physical activity. So this is the problem for our whole body and the brain, and hypercortisolaemia is the main aetiological factor for depression. We have immunological changes in our brain. They last many months. I have patients who have been depressed for many years or many months. They don’t know: ‘What happened to me?’, ‘I started to be sad’, ‘I have problems with my sleep’, ‘I have anhedonia, apathy, anergia, I feel pain’. We should talk about it. If we have hypercortisolaemia, we have elevated level of interleukins. Interleukins are inflammatory cytokines. So we decrease the level of noradrenaline and serotonin in the brain, and that’s why we feel more pain than before the depression.

So we have many patients who go from one doctor to another, from a cardiologist to a gastrologist, from a gastrologist to a neurologist. And they try to diagnose, they try to find out what’s happened to me, and if they come to a psychiatrist, we prescribe the drugs and they improve.

Ante Silić: After the era of tricyclic or tetracyclic medicines, which were cardiotoxic and everything, came the era of SSRIs, which was a perfect era because we reduced the side effects, but we didn’t improve the efficacy. And then finally, we have new dual multimodal and add-on drugs for treating depression. What in your opinion, primarily as a clinician, as a practitioner, would be the first line? Where do you see the typical new-age patient with the first line therapy?

Piotr Wierzbiński: A very good question, because we should focus on the patients, and we should analyse the symptomatology because we know that if you have lower serotonin levels in the brain, you feel more anxious, you are impulsive, you suffer from suicidal thoughts, sexual dysfunction, and you get irritated very quickly. But if you have lower noradrenaline levels in your brain, you suffer from lack of energy, fatigue, cognitive dysfunction, and you feel more pain. If you have a high level of noradrenaline, your pain threshold is high. So in my opinion, nowadays we have more patients with fatigue, anergia, apathy, patients that have no battery, as I said. So this is the problem, because most of us, most psychiatrists, think about anxiety as the first line. Anxiety as mood.

Ante Silić: Exactly, exactly. That’s the issue.

Piotr Wierzbiński: So the first line treatment, for many years, has been escitalopram or sertraline or others. Look at this: you prescribed these drugs and after four months the people came back to you and said, ‘My God, doctor, it’s quite good. But you know, I have no energy. I have difficulties concentrating, my planning is not good. What’s happened to me? In the morning, I feel better.’ So this is the proof that we should think about SNRIs. We should think about antidepressant drugs that increase the two neuromediators, serotonin and noradrenaline. And why? Because this patient should be treated with SNRIs, because his symptomatology is for SNRIs. We have two SNRIs on the market, venlafaxine and duloxetine, and what is the main difference between the two drugs? Duloxetine is stronger and much easier to prescribe to the patients because, usually, an effective dose is 60 milligrams. If you think about venlafaxine, you should prescribe 375 milligrams to patients. This is the equivalent dose to 60 milligrams of duloxetine. Risk of hypertension and side effects could occur more often than in duloxetine. Because duloxetine – if you prescribe 60 milligrams, for example, you increase serotonin because duloxetine is a strong serotonin reuptake inhibitor and a strong noradrenaline reuptake inhibitor. So you increase serotonin and noradrenaline and you achieve improvement in anxiety and in lack of energy, low mood, and apathy. So this is important in how we choose drugs: analyse the symptomatology because, based on monoamine hypothesis, we know that disbalance in serotonin, noradrenaline and dopamine is responsible for the main symptomatology. Many of our patients suffer from low mood, cognitive dysfunction and suffer from anxiety and lack of energy.

Ante Silić: Exactly. I think that, again, one thing that I would like to point out is – tell me if you agree or disagree, absolutely – that we should not fall into the trap of pronouncing that, exclusively, any class of antidepressants or drugs that show antidepressant activity, whether they are antipsychotics, mood stabilisers or any other, are the sole and exclusive first line. So basically, we are coming to an era where any antidepressant should be considered a first line.

Piotr Wierzbiński: I agree with you. If you compare the efficacy in meta-analyses or randomised control studies, the efficacy of two classes is similar, but if you compare true efficacy based on meta-analyses, you have SNRIs as more efficacious drugs than SSRIs. Why? Because most patients have dual symptomatology, not pure serotoninergic symptomatology. We have more patients with noradrenergic and serotoninergic symptomatology. So for me, if you ask me what the first line treatment is, every drug is equal, but a better response comes from SNRIs because two neuromediators are stronger than one neuromediator. And clinical practice shows that.

Ante Silić: Exactly. I couldn’t agree more because we are maybe undertreating if we are just looking at one class and one molecule as the first line and losing time. Definitely, the guidelines should be there, but not as something that we cannot be creative about.

Piotr Wierzbiński: For me, the important things are compliance and the relationship with the patients. So if I prescribe SSRI or if I choose SNRI, the time from the onset of the treatment to the onset of the drug’s action is much better in SNRIs.

Ante Silić: It should restore compliance and therapeutic alliance if the improvements show up faster rather than later. If you had to wrap up or conclude this talk that you just gave in a couple of sentences, what would be the most important points?

Piotr Wierzbiński: The key facts for our practice are: we should describe the patient and we should choose the drugs based on symptomatology. So we should define the patients and describe the symptoms.
You need more serotonergic drugs or more noradrenergic drugs or you need both. The next step is adequate doses. We should remember that our drugs, the modern drugs, are quite safe, but we should prescribe adequate doses because too small a dose is not effective. Usually doctors have the tendency to prescribe lower doses. For me, adequate doses are 60 milligrams of duloxetine or higher. The third point is that we should focus on the patient and compliance, use adequate doses, and explain to patients that in some cases you should wait for the drugs.

Ante Silić: Perfect. I couldn’t agree more, again. I must say that, what comes to my mind is that we have chosen a pretty demanding job, both of us. So thank you, Piotr, for this wonderful and insightful conversation.

Piotr Wierzbiński: Thank you for a nice talk. It was my pleasure.

Ante Silić: Thank you for following this Krka talk, and be sure to stay tuned for the next one.

Balancing the two poles: Discussion of two psychiatrists on bipolar disorder treatment

In this episode, we discuss bipolar disorder, previously known as manic depression. It is characterized by periods of depression and periods of abnormally elevated mood that each last from days to weeks. The right diagnosis and treatment of bipolar disorder remain one of the biggest challenges in everyday psychiatric practice. There are numerous considerations that have to be involved in making a differential diagnostic procedure as well as in the treatment decision-making process.

Assoc. Prof. Ante Silić, MD, PhD, Croatia

Ante Silić is Associate Professor at the School of Medicine at the Catholic University of Croatia. He is subspecialized in social and biological psychiatry and works at University Hospital Centre Sestre Milosrdnice, Zagreb. He is focused on psychiatric research and everyday clinical practice.

Piotr Wierzbiński MD, PhD, Poland

Piotr Wierzbiński holds a private medical practice in Lodz, Poland. As part of his research development he participated in internship at the Department of Mental Health, University of Siena School of Medicine, Italy. He is the author of over 80 medical publications including those involving panels on epidemiology and pharmacotherapy in psychiatry, sports psychiatry, suicide, and on the overlapping fields of somatic medicine and psychiatry.

Ante Silić: Do you know that sometimes it takes up to ten years or even more for the proper diagnosis of bipolar disorder to be established?

Piotr Wierzbiński: Hello, everyone, I’m Piotr Wierzbiński. I’m a psychiatrist from Poland, from Łódź – it’s a big city centre of Poland. It’s a great pleasure for me to introduce Professor Ante Silić from Croatia, from Zagreb, a big city in Croatia. Everyone in Poland knows where Croatia is because it’s our favourite holiday destination. Now, we are going to talk about bipolar disorder because it’s a very interesting disease and the epidemiology of bipolar disorder is quite interesting. We’ll talk about pharmacology and we’ll talk about all interesting things for our clinical practice.

Ante Silić: Thank you for this kind introduction. I feel very humbled to be in your company here. Yes, you said it right. We’ll talk about bipolar. I find it a very important and interesting topic because it is probably one of the diagnoses that are most commonly, I would say, missed.

Piotr Wierzbiński: I agree with you because we have many patients who suffer from unipolar depression and they have no unipolar. They suffer from bipolar depression. So could you explain to us and say something about the predictive factors for bipolar depression? Because in routine practice, in normal clinical practice, usually we see depression patients.

Ante Silić: We do have to be aware of the fact that bipolar patients present themselves to us and they seek contact for help mostly while being depressed. They do not feel like they need help while they are manic. And then, there is also that important period of time when they are asymptomatic. They don’t suffer from any symptoms. So it is kind of self-explaining why we do make that error in judgment or differential diagnosis. Because in the split in time, in the clinical presentation of a depressed patient who is uni- versus the one who is bipolar, there are virtually no differences. There can be two identical patients, one suffering from unipolar, the other one from bipolar disorder at the split time, in the moment. But with all the anamnestic and hetero-anamnestic data, with all the questions that we should ask, the checklist that you actually asked me about – it is something that we should ask our every patient, every time. Whether they have experienced periods when their mood was elevated a little bit more than usually, a little bit more than normally, which is a difficult question because nobody thinks that mood is too high. Everybody enjoys it and everybody misses it once it passes. But still, that’s the area where we can profit from the data that our patients’ spouses or brothers or sisters or children or coworkers will give us. And then with that question asked also an important one should be there such as the onset of the symptoms. The earlier they start, the higher the risk that the patient suffers from bipolar versus unipolar. Psychoactive substance abuse, also an important question. There is some, let’s call it self-medication in the area of unipolar but the numbers are much, much higher for bipolar. Then comorbidity, such as personality disorder, or also some comorbidities with some schizophrenia spectrum disorders. Because bipolar is somewhere in the spectrum, somewhere between unipolar or schizoaffective disorder. And as such, it can have its highs and lows.

Piotr Wierzbiński: And if we observe the natural history of bipolar, so the hypomanic episodes or manic episodes are rather shorter and the depressive are longer.

Ante Silić: Yes, more impressive.

Piotr Wierzbiński: Yes. Do you think that this is a problem for diagnosis? Because people don’t want to say to their doctors that they have transient hypomanic episodes. This is a problem.

Ante Silić: I think that they don’t see it. There is such an issue in this important topic, in this area, it is stigma. But stigma of bipolar is a little bit, significantly higher than the one of addiction to alcohol, than the one of pure depression, unipolar depression, because many, let’s say celebrities, have spoken openly about addictions, about depression, but not so many about other psychiatric disorders.

Piotr Wierzbiński: What about suicidal rate in unipolar versus bipolar depression? Could you explain this to us? Because this is the serious problem, I think.

Ante Silić: Absolutely. That’s one of the most important differential diagnostic issues. We are not persisting in being as precise as possible, as early as possible, just so that we can be academically clean or therapeutically clean. We are insisting on that area because the risks related to a wrong or delayed or even never established diagnosis in bipolar is directly linked to the high rate of suicide attempts and unfortunately of successful attempts. So that that’s something that should be taken into consideration very early on.

Piotr Wierzbiński: Everyone knows that your passion is neuropsychopharmacology and the receptors, etc. So tell us something about the treatment, because the treatment could be very effective. If our patients with bipolar are treated with effective drugs, long-term treatment could be very effective and improve the quality of life. Tell us something about the drugs.

Ante Silić: Yes, thank you. That’s my favourite area.

Piotr Wierzbiński: I knew it.

Ante Silić: After differential diagnosis. We have to think early on in the treatment about the long-term outcomes, about the results that we want to achieve, about the functionality and recovery and prevention of suicide. So lots of things to think about. The logical question that arises is, is there a drug that can actually combine and check all the boxes, especially because we do prescribe antidepressants in bipolar disorder. This is one of the areas that are very much debated upon because, literally, if you look by the book, you wouldn’t be allowed to do so. But our patients suffer. Our patients are depressed even though they are bipolar. But we should kind of visualise it in a way that antidepressants maybe do have a place in the treatment of bipolar, but a very narrow one. Also, the next maybe logical step would be a mood stabiliser, but it covers not so big an area as an atypical antipsychotic. The widest area is covered with, for example, quetiapine, which covers both, manic and depressive phases, which is a good mood stabiliser and which can actually cover short-term outcomes to mid- and even long-term ones.

Piotr Wierzbiński: Why is quetiapine effective in bipolar?

Ante Silić: I would say that the molecule is built in such a way that it has different affinity and different effect on different receptors regarding the dose and regarding the formulation − there is the immediate release and extended release. So basically, in bipolar – I mean you cannot generalise, and there is no single rule that fits everyone. You always use individualised approach to the patient obviously – but in some mid- and high-range doses, it covers even dopamine for psychotic levels of symptoms, either manic or depressive ones. It covers serotonin reuptake, noradrenaline reuptake, if you are thinking about the active metabolite of quetiapine, and it covers also the H1 receptor. So, it’s a polypragmatic molecule in one molecule. I have a lot of, a high amount of good experience with quetiapine in this area of therapy. So basically, all the bases are covered. So that that should answer your question. I think so.

Piotr Wierzbiński: You know that many people who suffer from bipolar disorder ask us, psychiatrists, ‘Should I take these drugs all my life?’

Ante Silić: Well, people resent the idea of psychotropic medications, each and every one, especially if we are talking about psychotropic medication that should be taken long term. And once the bipolar has started rolling, it’s close to a lifetime. A huge issue in bipolar is also compliance. That comes together with the lack of insight, and with stigma and with everything that we tackle, all of those issues during the treatment process. But yes, it’s a long-term therapy. And then I draw a lot of analogies when I try to explain to each and every patient, how long will it be. I said, for example, I’m taking a hypertension medicine. And I did not ask my cardiologist how long. Most probably a lifetime. Maybe they will change it at one point to something else or not. But I trust my cardiologist and I’m doing regular checkups and I take my medications and so. It resonates differently with different kinds of patients. But still, it helps a lot to be very, very personal in the approach, in the explanation, and in answering that important question.

Piotr Wierzbiński: Tell us … what about the patients who drink alcohol, use many substances and the interactions. People ask me, ‘Is it a serious interaction or not, doctor? What can you tell me?’

Ante Silić: If they come to the point when they ask a specific question about interactions with alcohol or THC or whatever illegal or legal substance they are talking about, they asking for a friend. They’re not asking for themselves. That’s a start. We should have a good rapport. We should have as honest, as clear communication as possible. But we should be aware that patients, most of the time, will not share all the details or at least that we do not understand them correctly. How much confidence does a patient have at each point to share important details is a different story. We are trying to limit benzo prescription rates in Croatia, which are sky-high, through the roof. But still, basically everybody takes benzodiazepines these days. So psychoeducation, therapeutic alliance, honesty and patience, that’s something that usually works.

Piotr Wierzbiński: To conclude, let’s make a summary. The key important facts about bipolar disorder useful for our routine, our practice.

Ante Silić:  If I had to summarise in a couple of sentences, maybe the first thing that would be of importance is to think early on about the possibility of bipolar diagnosis, even when somebody presents as depressed, as unipolar, and ask every patient, every family, every time in order to differentiate that. And then, after that, I think the second most important thing would be to think about long-term treatment and long-term outcomes early on in the treatment because we do have the luxury of having a huge range of psychopharmacs. So we tend to sometimes aim and shoot at the symptoms and not maybe think about the long-term outcomes. In this context, I would say that the story about using antipsychotics as mood stabilisers should come early on in the treatment, thinking about the long-term outcomes. And thirdly, but not least importantly, to have in mind why we are doing all that, because the quality of life is awful for bipolar patients, especially in depressed phases, and to have in mind the huge risk of suicide. Basically, that are very important topics about bipolar that I would like to underline.

Piotr Wierzbiński: Thank you for a nice talk. Thank you for everything and see you soon. You can watch us in another podcast. I think so.

Ante SilićThank you very much.

Modern-day depression and anxiety: Easing the burden on the back of real-world evidence

Depression and anxiety are a great hidden burden in our society, and the presence of medical comorbidities further increases it. The COSMOS study provided a detailed view into the management of comorbid diseases in clinical practice in four countries of South East Europe. It also revealed the data on patient management of depression that can be used as a base point for optimising the clinical management and patient outcomes, and improving the patients’ quality of life.

Assoc. Prof. Milan Latas, MD, PhD, Serbia

Milan Latas is Associate Professor of psychiatry at the Clinic of Psychiatry at the Faculty of Medicine of the University of Belgrade. He is the author of numerous medical publications with over 130 citations. In his work, he focuses especially on anxiety disorders and depression, emphasising comorbidities as well as the quality-of-life issue in these groups of patients. He acted as the international coordinator for the real-world evidence research Cosmos.

Assoc. Prof. Ante Silić, MD, PhD, Croatia

Ante Silić is Associate Professor at the School of Medicine at the Catholic University of Croatia. He is subspecialized in social and biological psychiatry and works at University Hospital Centre Sestre Milosrdnice, Zagreb. He is focused on psychiatric research and everyday clinical practice.

Milan Latas: Don’t be focused just on diagnosis, just one problem in your patients. Comorbidity is a rule rather than an exception.

Ante Silić: Hello and welcome to yet another Krka talk. My name is Ante Silić. I’m a psychiatrist from Zagreb University Hospital Sestre Milosrdnice. I am proud to announce and host Professor Milan Latas, my dear colleague and friend who I’ve known for years now, who I’ve admired for his writing skills, his editorial skills, his publishing skills. Today, we will be primarily talking about depression, about anxiety, about comorbidities. I think it’s a rather important subject because we are kind of drilled through classification systems to think in terms of one diagnosis per patient. So what would you say about these comorbidities, anxiety and depression?

Milan Latas: First of all, dear Professor, dear Ante, thank you for those words that you said to me. Comorbidity could be a huge problem in psychiatric practice because it’s very common that we focus only on one disorder or one problem, which a patient can tell us about and which bothers him the most. But the problem is that some patients don’t have only one disease or only one disorder. They usually have more than one disorder. That could be a problem in the diagnostic view but also in the therapeutical view. If we don’t ask a patient about the presence of some other problems or diagnostic problems, we cannot give him good therapy and he will not get well, better, or the way he used to be.

Ante Silić: Exactly. That’s the issue for most psychiatrists or probably the other branches of medicine, but we are not anything else than psychiatrists. Basically, the DSM system or ICD system only at one point, as far as I know, included the axis system, which allowed us to code and include comorbidities in a more logical way. Now, we are still deciding for one, and of course, nobody forbids us to write more. But still, how often would you say anxiety coexists and is comorbid with depression and vice versa? And what would be the best therapeutic approach to a person suffering from both, from depression and anxiety?

Milan Latas: Previous research studies said that comorbidities are rather a rule than an exception, that most patients with depression or anxiety disorders also have two or more psychiatric disorders, but also have comorbidities with somatic disorders or diseases. We did the research study COSMOS. That was an international epidemiological study that included patients from Croatia, Bosnia and Herzegovina, North Macedonia and Serbia. More than 2,000 patients were included in the sample, and we researched their diagnosis. We asked them about comorbid conditions, conditions that occurred almost at the same time as the indexed disorder, with primary disorder. Then the problem is that more than half of patients with depression also have some other diagnosis, mostly anxiety disorders, especially generalized anxiety disorder. But they also have some somatic problems, like circulatory diseases, like endocrine diseases. The same situation was in the sample of anxiety disorder patients. Most of them also have depression. About half of them had depression, which could be a problem if, in anxiety disorder, it takes a long time for the patient to get treated, to get better. And depression came as a resultant of anxiety disorder. Also, patients with anxiety disorder, mostly with generalized anxiety disorder or panic disorder, have some other somatic diseases as co-occurring disorders with psychiatric problems.

Ante Silić: COSMOS is actually the first study, at least as I’m aware of, that kind of relates to Scandinavian registry-based studies that actually showed us sobering results about what comorbidities mean in terms of shorter life expectancy for our patients. Primarily, the first published results from Scandinavian registry-based studies were those covering increased mortality in schizophrenia patients. So this probably, at least I think so, is the inspiration for COSMOS that you’ve done through the multi-regional study. Do you have any unpublished data about the therapy or how the therapeutic approach in COSMOS came out in the results?

Milan Latas: We wrote a paper, and we did it for reviewing. It’s actually in the reviewing process. Those data indicate, as we expected, that antidepressants were the first line in patients who were treated for depression and also patients who were treated for anxiety disorders. They also get some anxiolytics, benzodiazepines, some of them get antipsychotics. But we are talking about antidepressants. The SSRIs are the first-line treatment, and they are most frequently used. When we’re talking about SSRIs, escitalopram was the main medication used in patients with depression, but also in patients with anxiety disorder. The second line was sertraline. The difference between depression patients was not so huge, 29% escitalopram versus 27% sertraline. In anxiety disorder, the discrepancy was much smaller but present. Escitalopram was used in one third of patients, and other antidepressants were used in a much smaller number of patients.

Ante Silić: That’s why I gave you the introduction I gave you. Because your papers actually correlate with my practice, with my everyday clinical practice. Because we often find ourselves reading a paper that suggests this and that, and then you don’t relate to it in clinical practice, at any level. But this one actually does.

Milan Latas: Yes, that was an epidemiological study in four countries and 2,000 patients. We did the research in the field. Both, psychiatrists or no psychiatrists really worked with those patients, and that was the result of the study.

Ante Silić: From your clinical practice, for a patient that has comorbidity of depression and anxiety disorder, what would be your most prescribed dose of escitalopram? Would it be 10, would it be 5, would it be 20 mg?

Milan Latas: It depends on the patient and his clinical presentation. If he is more depressed or more anxious, the dose has to be 15 or 20 mg, not far from 20 mg. For sertraline, it is 100, maybe 200 mg per day. Some patients have to get benzodiazepines, of course in the first days or weeks of treatment, to get better. After that, we cut them off.

Ante Silić: What was your experience, within the study or out of it in the clinical practice, with pregabalin for anxiety disorders in comorbidity with major depression?

Milan Latas: Pregabalin is not indicated for patients with major depression. It could ease the symptoms of anxiety in patients with depression but it is not the first line for patients with depression. We can also give it to patients with generalized anxiety disorder. Pregabalin is the first-line treatment at dosages of about 150 mg as the starting dose to 300 or 450 mg per day for those patients, two times a day early in the morning and in the evening.

Ante Silić: So to profit more from your past clinical and publishing experience … How long do you wait before raising dose, before changing the drug or molecule? For example, you start with 10 mg of escitalopram?

Milan Latas: I usually start with 5 mg. If we are talking about escitalopram, I usually start with 5 mg for six days. After that, I increase it in every patient to 10 mg. I see the patient about 10 days after the initial treatment and just look at side effects. First of all, does he have side effects from the therapy? And after two, three, maybe four weeks, I check the clinical picture for improvement. If he shows improvement, I don’t change the dosage. If he shows small improvement, I increase the dosage to 15 mg or I often increase it from the starting 10 to 20 mg. But if he doesn’t show any improvement, I switch to another medication.

Ante Silić: If you had to wrap up and make a couple of conclusions about today’s talk, what would those be? What would be the main points?

Milan Latas: The main points from my clinical point of view and based on the results of the COSMOS study are that comorbidity or co-occurrence of disorders could be a huge problem. First of all, for the patients, and after that for us, for psychiatrists or neuropsychiatrists. Because if we don’t look at the broader picture, if we just focus on one disorder, we cannot get proper diagnosis, and after that we don’t have proper treatment for that patient.

Ante Silić: And regarding COSMOS – it also covered the same story.

Milan Latas: Yes, the results are in line with the clinical practice.

Ante Silić: As we concluded earlier. Perfect. Thank you very much. And now, I have another question for you if you don’t mind. How do you balance all these obstacles that are in front of you in the professional part of your life with those in your private life? This job can be overwhelming sometimes.

Milan Latas: Yes.

Ante Silić: How do you manage? What do you do? What’s your secret?

Milan Latas: I have two secrets. I train a lot. I train for triathlon, swimming, running and cycling. And the other is that I like to get my friends out of psychiatry and encourage them every day to make an appointment, go for a walk or maybe do some training, or go for a drink, coffee or something like that.

Ante Silić: Thank you very much, very good advice, two of them at least. Thank you for this interview, for sharing your knowledge. And thank you for following this episode of Krka talks and hope to see you for the next one.

Functional recovery as a main treatment goal in mental disorders: Overcoming functional limitations in mental disorders

Mental disorders severely affect the daily functioning and quality of life of patients and also of their relatives. In recent times, we observe a shift in mental health treatment goals, from a symptom-focused approach to individualised medication selection that seeks to restore patient’s everyday functioning, such as work productivity, social relationships and ability to live independently, and improve their quality of life.

Assist. Nuša Šegrec, MD, PhD, Slovenia

Nuša Šegrec is a psychiatrist working at the National Centre for the Treatment of Drug Addiction at the University Psychiatric Clinic in Ljubljana, Slovenia. Her primary clinical work focuses on the treatment of patients with complex needs – substance use disorders and comorbid mental health disorders. She is also one of the active members of Coordination of Centres for the Prevention and Treatment of Drug Addiction at the Ministry of Health of the Republic of Slovenia.

Assoc. Prof. Ante Silić, MD, PhD, Croatia

Ante Silić is Associate Professor at the School of Medicine at the Catholic University of Croatia. He is subspecialized in social and biological psychiatry and works at University Hospital Centre Sestre Milosrdnice, Zagreb. He is focused on psychiatric research and everyday clinical practice.

Nuša Šegrec: It is estimated that almost 165 million people suffer from mental disorders every year in Europe.

Ante Silić: Welcome to Krka talks on the topic of mental health. My name is Ante Silić, I’m a psychiatrist. I work at the University Hospital Sestre Milosrdnice in Zagreb. Today, I’m proud to host and to present to you my dear colleague Nuša Šegrec, also a psychiatrists, working also in the field of dual diagnosis. We will be talking about mental health, about the difference between recovery and remission, about dual diagnosis, and what it actually means. So the podium is yours.

Nuša Šegrec: Thank you. Yes, I mostly work with patients with dual diagnosis. I think recovery and this question of recovery fits into this topic because this is very complex. These are patients with very complex needs. We always want recovery, but we need many steps to do that and to achieve, to reach the recovery we actually want.

Ante Silić: When we say dual diagnosis, I think that most young psychiatrists or residents do not grasp the idea what duality actually means. It’s a comorbidity of this and that. Can you explain that to us a little bit?

Nuša Šegrec: Yes, I think it’s an older term. I don’t like it, because people are not diagnoses. I think that it’s a little bit stigmatising. We always try to find a better word. In the Slovenian language, we didn’t find a good word for these patients. We try to at least say these are patients with the comorbidity of one mental disorder and another. But in the Anglo-Saxon world, they mostly use the term ‘patients with complex needs’. And I think it’s less stigmatising and actually says more. That means that someone has substance use disorder and comorbid mental disorder. This ‘complex needs’ term comes from complex needs of these patients, because they really have different areas that can be affected by the disease. This is in short what dual diagnoses are. We also use the term multiple diagnosis because they also have somatic disorders.

Ante Silić: It’s usually more than two. Another word that I would like to talk to you about is recovery. We have been using that word … It is not that long since we’ve started to use it. Is it because we have the luxury to use it now or are we trying to change things? What’s happening with recovery? What is … How is recovery different from remission?

Nuša Šegrec: How is recovery different from remission? Yes. We have to focus on different phases of the treatment if you agree. Of course, we want symptomatic recovery. We want for the patient that symptoms are relieved, that he’s not so much under their influence, because they affect everyday living. We all know that. But it’s not the symptoms we want to get rid of, if I can say so. Recovery is much more. Of course, it’s a very personal term because we don’t have this medicine anymore, I hope so, a one-fits-all, but we need to go for more personalised medicine. Of course, we can talk in general about recovery, but I think for every patient it is very important to have his own goals short term, long term, and then try to achieve some changes. Of course, we all want premorbid recovery or an even better functioning but we have to be realistic.

Ante Silić: Exactly. The key is, as I see it, in that added value. We are not just teaching and helping patients up to the point where they can somehow function. We are aiming for full functionality, whatever on the individual basis that means for each individual patient. Sometimes, we, as professionals, have different expectations about the treatment than our patients. I would say maybe most of the time. How to make amends between those two different goals?

Nuša Šegrec: I remember this study, now that you mention this area. There was a study about healthcare professionals’ and patients’ expectations in the treatment by different phases of major depressive disorders, in the acute and then in the following phases. In the acute phase, mental health providers were more focused on symptom reduction. And I think, if you agree, we do this in practice. I always try to help patients to relieve maybe insomnia or inappetence, if they don’t have appetite, or in psychosis if they have acute psychotic symptoms. So this is our focus. But when they looked into the patients’ expectations in the acute phase, they were different because they also want this functional recovery. So, return to work, good relationships with the family, social life – they want to improve that. In the acute phase, there are differences. But in the second phase, when the progress is achieved, the goals are similar.

Ante Silić: Eventually, we find common ground, but it takes some time. It’s good to know. I think I know the study that you are mentioning because it was rather surprising to me that, sooner than us, our patients look for functional recovery and long-term outcomes, and we are focused on the leading symptom. And we think we are both right. But we should be aware of this one, because by actually addressing that and just explaining, psychoeducating our patients that we do have the same goals but maybe not sorting them out on the same scale – that helps a lot and eases the tension in most of my patients, at least if we get the time to talk about it. Another interesting question that I think should be addressed is: When we look at the global burden of disease, where is mental health today? Has it finally found its place? Unfortunately, on the top, or not?

Nuša Šegrec: Mental health is an integral part of health. We agree with the definition of the World Health Organization, and we agree probably that there is no health without mental health. But unfortunately, there is a high percentage of mental health disorders among European Union citizens estimated. It’s estimated that almost 165 million people in one year have symptoms of mental illness. That is a very high number. Do you agree?

Ante Silić: Yes, absolutely. The World Health Organization gave us that definition, ‘There is no health without mental health’, and that’s a good one. But it was just a theory. Now, we are bringing it closer to the practice. I think that they predicted that by 2020 it would have been at the second place, but it surpassed the expectations, unfortunately, again. Probably, the reasons are not only global economic, political and geopolitical turmoils, wars and other things, but also the COVID pandemics that hit us in places that we didn’t expect that much. Because, if I recall correctly, you mentioned that adolescents were hit the most by the COVID pandemics and, globally, we are getting there.

Nuša Šegrec: One of the most, yes.

Ante Silić: So, we are getting there. We are recognising the needs and the resources that have to be invested into treatment and recognition, diagnostics, individual approach.

Nuša Šegrec: I agree absolutely.

Ante Silić: Same here. Thank you very much for sharing these insights and thoughts with us. If you had to conclude and give us final thoughts about the topics that we covered today, what would they be?

Nuša Šegrec: I think that it’s very important that we start with a good diagnostic procedure in every patient, with screening, diagnosis, individual goals with the patient. We are a team. We are not alone. We have to involve, as much as possible, important others, of course if the patient wants. We have to involve other specialists, other professionals. Now, we have such good programmes, I’m talking about integrative treatment programme, which we can say is a holistic approach to treatment to achieve functional recovery. We have plenty of opportunities. We have to be aware of all factors that can reduce the success of recovery. We have to be very patient with our patients because we have patients with chronic diseases, and sometimes these steps are very slow, even though we want very, very fast changes.

Ante Silić: Thank you very much.

Nuša Šegrec: Thank you.

Ante Silić: And thank you for following this Krka talk, and hope to see you for the next one.

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