The Prozac generation. How they hid the truth about antidepressants from us

Indications

◊ Ministry of Health of Russia

F32 Depressive episode

F41.2 Mixed anxiety and depressive disorder

F42 Obsessive-compulsive disorder

F50.2 Bulimia nervosa

◊ FDA recommendations

Major depressive disorder (adults and children over 8 years of age)
OCD (in adults and children from 7 years old)
Premenstrual dysphoric disorder
Bulimia
Panic disorder
Bipolar depression (in combination with olanzapine)
Resistant depression (in combination with olanzapine)

◊ Recommendations from UK Medicines and Healthcare Products Regulatory Agency

Major depressive episode (adults and children over 8 years old only if 4-6 psychotherapeutic sessions have not produced results)
OCD
Bulimia (in combination with psychotherapy)

◊ Using Off-label

Fibromyalgia
Migraine
Raynaud's disease
Hot flashes caused by hormonal chemotherapy [4]
Selective mutism
Mild agitation in dementia
PTSD
Social anxiety disorder [6]

Fluoxetine

Fluoxetine

(eng.
fluoxetine
) - an antidepressant, a selective serotonin reuptake inhibitor.

Fluoxetine is a chemical compound

Fluoxetine as a chemical is (RS)-N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine. Propylamine derivative. The empirical formula of fluoxetine is C17H18F3NO. Molecular weight 309.3 g/mol.

Fluoxetine is a drug

Fluoxetine is the international nonproprietary name (INN) of the drug. According to the pharmacological index, fluoxetine belongs to the group “Antidepressants”. According to ATC, fluoxetine is included in the group “N06 Psychoanaleptics” and has the code N06AB03. Fluoxetine is also a trade name for a drug.

Indications for use of fluoxetine

Fluoxetine is indicated for use in:

depression of various origins, especially those accompanied by fears
obsessive-compulsive disorders
bulimic neurosis

Experience with the use of fluoxetine in the treatment of functional heartburn

The American Gastroenterological Association's updated functional heartburn guidelines (2020) note that fluoxetine is the only selective serotonin reuptake inhibitor studied in the treatment of functional heartburn. Patients with refractory heartburn that persisted while taking omeprazole and negative endoscopy were randomized into three groups to receive different treatment options: a) double dose of omeprazole; b) omeprazole and fluoxetine 20 mg per day; c) omeprazole and placebo. Those who received fluoxetine showed a significantly greater increase in heartburn-free days (mean 35.7 days) compared to those who received double-dose PPI (mean 7.14 days) and placebo (mean 7.14 days) . This superior therapeutic effect of fluoxetine was observed only in a subgroup of patients with normal pH values (Fass R, Zerbib F, Gyawali CP).

Indications for the use of fluoxetine in the treatment of obesity

The World Gastroenterological Organization includes fluoxetine in the list of drugs used in the treatment of obesity in patients with a body mass index of at least 27 kg/m2 (BMI. Obesity. Practical recommendations) and at least one of the following:

sleep apnea
night meals
bulimia

Currently, fluoxetine is the drug of choice for the treatment of obesity in patients with depression who require both an antidepressant and a weight loss drug. The drug is not used for the treatment of obesity, since during long-term observation (12 months) doses 2-3 higher than usual doses of antidepressants were required to achieve weight loss. The effect was observed only for 6 months, and then a reverse increase in body weight occurred, despite ongoing treatment. A number of side effects were revealed - asthenia, increased sweating, nervous agitation, tremor, sexual dysfunction (Butrova S.A., Plokhaya A.A.).

How to take fluoxetine and dose

Fluoxetine is taken with food, orally, in 1-2 doses per day, preferably in the first half of the day.
The initial daily dose of fluoxetine is 20 mg. If necessary, the dose of fluoxetine is increased weekly by 20 mg per day. The maximum daily dose of fluoxetine is 80 mg, for the elderly - 60 mg. Duration of therapy is 3-4 weeks, for obsessive-compulsive conditions - 5 weeks or more, for bulimia nervosa - 1 week. The maintenance daily dose of fluoxetine is 20 mg. Fluoxetine is not recommended to be taken concomitantly with monoamine oxdase inhibitors (MAOIs), such as furazolidone, rasagiline (Azilect), selegiline (Yumex, etc.), isocarboxazid, phenelzine, procarbazine, tranylcypramine and others, or if MAO inhibitors were taken within the previous two weeks. With the simultaneous use of fluoxetine and MAO inhibitors, severe, sometimes fatal, reactions are possible, including hyperthermia, rigidity, myoclonus, autonomic disturbances, extreme agitation progressing to delirium and coma. Due to the prolonged elimination of fluoxetine, a gap of at least 5 weeks or more is necessary between stopping fluoxetine and starting an MAOI.

Side effects of fluoxetine

Side effects of fluoxetine therapy:

very often: diarrhea, nausea, headache, insomnia,
often: dry mouth, dyspepsia, vomiting, anorexia, atrial flutter, hot flashes, impaired attention, dizziness, lethargy, drowsiness, tremor, nightmares, nervousness, tension, decreased libido, euphoria, sleep disturbance, itching, skin rash , urticaria, blurred vision, frequent urination, ejaculation disorders, erectile dysfunction, gynecological bleeding.
rarely: dysphagia, taste perversion, pain in the esophagus, hypotension, vasculitis, vasolidation, idiosyncratic hepatitis, muscle twitching, psychomotor agitation, hyperactivity, ataxia, incoordination, bruxism, dyskinesia, convulsions, depersonalization, hyperthymia, problems with orgasm, thinking disorders, manic disorders, tendency to bruise, cold sweat, priapism.

Use of fluoxetine during pregnancy, breastfeeding and children

Fluoxetine is not recommended for pregnant women, nursing mothers and children under 18 years of age.
Fluoxetine passes into breast milk, so breastfeeding should be discontinued during fluoxetine therapy. Fluoxetine is FDA Category C for fetal risk use in pregnant women (animal studies have shown adverse effects on the fetus and there have been no adequate studies in pregnant women, but the potential benefits associated with use of this drug in pregnant women may justify it use despite the risk).

Trade names of drugs with the active substance fluoxetine

The following drugs with the only active ingredient fluoxetine are (were) registered in Russia: Apo-Fluoxetine, Deprex, Deprenon, Portal, Prodep, Prozac, Profluza, Floxet, Fluval, Fluxonil, Flunisan, Fluoxetine, Fluoxetine HEXAL, Fluoxetine Lannacher, Fluoxetine Nycomed, Fluoxetine-OBL, Fluoxetine-Canon, Fluoxetine hydrochloride, Framex.
In Ukraine, in particular, Fluxen is registered (see instructions for use below). Brands of fluoxetine in the USA: PROzac, PROzac Weekly, Rapiflux, Sarafem, Selfemra, PROzac Pulvules.

Instructions for use of fluoxetine

Some instructions from manufacturers for the medical use of drugs containing the only active ingredient fluoxetine (pdf):

instructions for Ukraine (in Russian): “Instructions for the medical use of the drug Fluxen”, OJSC “Kievmedpreparat”
US instructions (in English):
“Prozac (fluoxetine hydrochloride) Pulvules for oral use. Prozac (fluoxetine hydrochloride) delayed-release capsules for oral use. Full Prescribing Information,” Eli Lilly and Company, January 2013.
"Fluoxetine tablets, 60 mg. Medication Guide,” Edgemont Pharmaceuticals, LLC. June 2014.

Fluoxetine has contraindications, side effects and application features; consultation with a specialist is necessary. Back to section

Mechanism of action and pharmacokinetics

Fluoxetine is a propylamine derivative. Fluoxetine, metabolized to norfluoxetine, selectively blocks the neuronal reuptake of serotonin in the brain, enhancing the actions of serotonin at 5HT1A autoreceptors. Fluoxetine is a weak antagonist of cholinergic, adrenergic and histamine receptors.

Maximum plasma concentration: 6-8 hours
Half-life 2-3 days
Metabolized by CYP2D6. Induces CYP2C9, inhibits CYP2C19, CYP2D6, CYP3A4.
Active metabolites remain in the blood for two weeks

Fluoxetine (Prozac, Profluzac, Prodep, Fluval, Flunisan, Portal)

Contraindications

Glaucoma, bladder atony, severe renal dysfunction, benign prostatic hyperplasia, simultaneous administration of MAO inhibitors, convulsive syndrome of various origins, epilepsy, pregnancy, lactation, hypersensitivity to fluoxetine.

Dosage

Initial dose: 20 mg 1 time/day in the morning; if necessary, the dose can be increased after 3-4 weeks. Frequency of administration: 2-3 times/day.

The maximum daily oral dose for adults is 80 mg.

Side effects

From the side of the central nervous system: anxiety, tremor, nervousness, drowsiness, headache, sleep disturbances are possible.

From the digestive system: diarrhea, nausea are possible.

From the metabolic side: increased sweating, hypoglycemia, hyponatremia are possible (especially in elderly patients and with hypovolemia).

From the reproductive system: decreased libido.

Allergic reactions: possible skin rash, itching.

Other: joint and muscle pain, difficulty breathing, increased body temperature.

Drug interactions

When used simultaneously with drugs that have a depressant effect on the central nervous system, ethanol may significantly enhance the depressant effect on the central nervous system, as well as increase the likelihood of developing seizures.

When used simultaneously with MAO inhibitors, furazolidone, procarbazine, tryptophan, the development of serotonin syndrome (confusion, hypomanic state, motor restlessness, agitation, convulsions, dysarthria, hypertensive crisis, chills, tremor, nausea, vomiting, diarrhea) is possible.

With simultaneous use, fluoxetine inhibits the metabolism of tricyclic and tetracyclic antidepressants, trazodone, carbamazepine, diazepam, metoprolol, terfenadine, phenytoin, which leads to an increase in their concentration in the blood serum, increasing their therapeutic and side effects.

With simultaneous use, it is possible to inhibit the biotransformation of drugs metabolized with the participation of the CYP2D6 isoenzyme.

When used simultaneously with hypoglycemic agents, their effect may be enhanced.

There are reports of increased effects of warfarin when used simultaneously with fluoxetine.

When used simultaneously with haloperidol, fluphenazine, maprotiline, metoclopramide, perphenazine, pericyazine, pimozide, risperidone, sulpiride, trifluoperazine, cases of the development of extrapyramidal symptoms and dystonia have been described; with dextromethorphan - a case of the development of hallucinations has been described; with digoxin - a case of increased concentration of digoxin in the blood plasma.

special instructions

Use with extreme caution in patients with impaired liver and kidney function, a history of epileptic seizures, and cardiovascular diseases.

In patients with diabetes mellitus, changes in blood glucose levels may occur, which requires adjustment of the dosage regimen of hypoglycemic drugs. When used in weakened patients while taking fluoxetine, the likelihood of developing epileptic seizures increases.

With the simultaneous use of fluoxetine and electroconvulsive therapy, the development of prolonged epileptic seizures is possible.

Fluoxetine can be used no earlier than 14 days after discontinuation of MAO inhibitors. The period after discontinuation of fluoxetine before starting therapy with MAO inhibitors should be at least 5 weeks.

Elderly patients require dosage adjustment.

The safety of fluoxetine in children has not been established.

During the treatment period, avoid drinking alcohol.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, you should refrain from potentially hazardous activities that require increased attention and rapid psychomotor reactions.

Pregnancy and lactation

Contraindicated for use during pregnancy and lactation.

Use in childhood

The safety of fluoxetine in children has not been established.

For impaired renal function

Contraindicated in severe renal impairment. Use with extreme caution in patients with moderate to mild renal impairment.

For liver dysfunction

Use with extreme caution in patients with impaired liver function.

Use in old age

Elderly patients require dosage adjustment.

Treatment regimen

◊ Dosage and dose selection

20-80 mg/day for depression and anxiety disorders
60-80 mg/day for bulimia
Depression and OCD: start with 20 mg in the morning and wait a few weeks if necessary increase to 80 mg
Bulimia: start with 60 mg in the morning, but you can start with a smaller dose
Due to the long half-life, changes in dosage will not be reflected quickly in blood concentrations; Accordingly, it is eliminated from the body longer than other drugs
Usually taken in the morning, but can be taken at other times of the day
The more anxious the patient, the lower the starting dose, the slower the dose is increased. In such cases, it is recommended to initially combine with trazadone or benzodiazepines [1].
If anxiety, insomnia, agitation, or akathisia occur at the beginning of treatment or after interruption of treatment, the possibility of bipolar disorder should be considered and switched to a mood stabilizer or an atypical antipsychotic

◊ How quickly it works

In some patients it begins to work immediately.
Begins to act after 2-4 weeks
If there is no effect after 6-8 weeks, you need to increase the dose or switch to another drug
To prevent relapse, it can be taken for many years.

◊ Expected result

Complete remission.
After the symptoms of depression disappear, you should continue taking it for one year if this was the treatment of the first episode. If this is to treat a recurrent episode, treatment can be extended indefinitely.
Use in the treatment of anxiety and bulimia can be indefinite [1].

◊ If it doesn't work

Change the dose, switch to another medicine or add an auxiliary drug;
Connect psychotherapy;
Review the diagnosis by identifying comorbid conditions;
In patients with undiagnosed bipolar affective disorder, the effectiveness of treatment may be low, in which case it is necessary to switch to a mood stabilizer [1].

◊ How to stop taking it

Gradual reduction is not necessary due to the long half-life of fluoxetine [1].

◊ Treatment combinations

For insomnia: trazadone
For fatigue, drowsiness, loss of concentration: modafinil [3].
Combinations with other antidepressants may activate bipolar disorder and suicidal ideation
The combination of fluoxetine + olanzapine has been very well studied, it gives excellent results in bipolar depression, resistant unipolar depression and psychotic depression.
For bipolar depression, psychotic depression, treatment-resistant depression, treatment-resistant anxiety disorder: mood stabilizers, atypical antipsychotics
For anxiety disorder: gabapentin, tiagabine

Prozac®

Suicidal risk

Depression is associated with an increased risk of suicidal ideation, self-harm (self-harm), and suicidal events. This risk persists until stable remission occurs. Since improvement may not occur during the first few weeks of treatment, careful monitoring by the attending physician is necessary until the patient's condition improves. Clinical practice shows that the risk of suicide may increase in the early stages of recovery.

Other psychiatric diseases for which Prozach® is prescribed may also be associated with an increased risk of suicidal events. In addition, these diseases can accompany major depressive disorder. Therefore, the same caution should be exercised when treating patients with other psychiatric illnesses as when treating patients with major depressive disorder.

Patients with a history of suicidal behavior who clearly exhibit suicidal ideation before treatment are at increased risk for suicidal ideation or behavior. These patients should be closely monitored during therapy.

A meta-analysis of placebo-controlled clinical trials of antidepressants used to treat psychiatric conditions in adult patients found that among patients younger than 25 years, antidepressant use is associated with an increased risk of suicidal behavior compared with patients receiving placebo.

Patients, particularly those at high risk of developing suicidal behavior, should be closely monitored, especially during the early stages of treatment and during subsequent dose changes. Patients (and their caregivers) should be warned to monitor for any clinical deterioration, monitor for the occurrence of suicidal behavior or thoughts, and unusual changes in behavior, and should contact their healthcare provider immediately if these symptoms occur.

Cardiovascular effects

QT prolongation may occur with fluoxetine, and ventricular arrhythmias or torsade de pointes (TdP) have been reported during post-marketing studies of fluoxetine. Fluoxetine should be used with caution in patients with congenital long QT syndrome, acquired long QT syndrome (for example, while taking fluoxetine with drugs that prolong the QT interval), if there is a history of indications of an increase in the duration of the QT interval in the patient's relatives, with other clinical conditions predisposing to the development of arrhythmia (for example, with hypokalemia, hypomagnesemia, bradycardia, acute myocardial infarction, decompensated heart failure) and with increased exposure to fluoxetine (for example, with reduced liver function). Patients with stable heart disease should undergo an ECG examination before starting fluoxetine therapy. If signs of arrhythmia develop during therapy, fluoxetine should be discontinued and an ECG study performed.

Skin rash

In patients taking fluoxetine, skin rash, anaphylactic reactions and progressive systemic disorders, sometimes serious involving the skin, kidneys, liver and lungs, have been reported. If a skin rash or other possible allergic reactions occur, the etiology of which cannot be determined, fluoxetine should be discontinued.

Epileptic seizures

As with other antidepressants, fluoxetine should be used with caution in patients with a history of seizures. Fluoxetine therapy should be discontinued if epileptic seizures develop in any patient. Also, fluoxetine therapy should not be prescribed to patients with unstable epilepsy; patients with controlled epilepsy require careful monitoring.

Electroconvulsive therapy

In patients receiving electroconvulsive therapy, prolonged seizures have been reported in rare cases while receiving fluoxetine. Caution is recommended when administering fluoxetine to these patients.

Mania

Antidepressants should be used with caution in patients with a history of mania/hypomania. Fluoxetine, like any antidepressant, must be discontinued if the patient is in a manic state.

Akathisia/ psychomotor restlessness

The use of fluoxetine leads to the development of akathisia, which is manifested by subjectively unpleasant sensations or restlessness, the need for constant movement, often without the ability to sit or stand still. Most often, such phenomena are observed during the first few weeks of treatment. In patients with these symptoms, increasing the dose of fluoxetine may have negative consequences.

Withdrawal symptoms

Withdrawal symptoms were common when fluoxetine therapy was stopped, especially when discontinued abruptly. In clinical studies, approximately 60% of patients developed various adverse events when therapy was discontinued, both in the fluoxetine group and in the placebo group. In the fluoxetine group, 17% of these events were severe, and in the placebo group - 12%.

The risk of developing withdrawal symptoms depends on several factors, including duration of therapy, dose, and rate of dose reduction. The most commonly reported symptoms were dizziness, sensory disturbances (including paresthesia), sleep disturbances (including insomnia and vivid dreams), asthenia, anxiety or agitation, nausea and/or vomiting, tremor and headache. Typically these episodes were mild to moderate in severity, but in some patients they could be more severe. In most cases, these phenomena resolve on their own within two weeks, but sometimes they can last longer (2-3 months or more). Therefore, withdrawal of fluoxetine therapy should be done gradually over one or two weeks, depending on the patient's needs.

Tamoxifen

Fluoxetine, as a potent inhibitor of the CYP2D6 isoenzyme, can lead to a decrease in the concentration of endoxifen, one of the most important active metabolites of tamoxifen. Therefore, fluoxetine should be avoided during tamoxifen therapy.

Weight loss

When using fluoxetine, patients may experience a decrease in body weight, however, this is usually proportional to the initial average body weight.

Hyponatremia

There have been cases of hyponatremia (in some cases, serum sodium levels were less than 110 mmol/l). Mostly, such cases were observed in elderly patients, in patients receiving diuretics and in patients with a decrease in circulating blood volume.

Diabetes

In patients with diabetes mellitus, hypoglycemia was observed during treatment with fluoxetine, and hyperglycemia developed after discontinuation of the drug. At the beginning or after the end of treatment with fluoxetine, dose adjustment of insulin and/or oral hypoglycemic drugs may be required.

Liver/renal failure

Fluoxetine undergoes extensive metabolism in the liver and is excreted by the kidneys. For patients with severe liver dysfunction, it is recommended to prescribe lower doses of fluoxetine, or prescribe the drug every other day.

When taking fluoxetine at a dose of 20 mg/day for two months in patients with severe renal failure (creatinine clearance < 10 ml/min) requiring hemodialysis, there were no differences in the concentrations of fluoxetine and norfluoxetine in the blood plasma when compared with patients from control group with normal renal function.

Midriaz

Mydriasis has been reported in association with fluoxetine. Caution should be exercised when prescribing fluoxetine to patients with elevated intraocular pressure or patients at risk of developing acute angle-closure glaucoma.

Hemorrhages

Ecchymosis, purpura and other similar disorders associated with increased bleeding have been reported with the use of SSRIs. Ecchymosis has been rarely reported. Other hemorrhagic phenomena (gynecological bleeding, gastrointestinal bleeding, etc.) were observed rarely. Caution should be exercised when treating fluoxetine, in particular in patients with concomitant therapy with oral anticoagulants and other drugs that affect platelet function (for example, with atypical antipsychotics such as clozapine, with phenothiazines, with most tricyclic antidepressants, acetylsalicylic acid, non-steroidal anti-inflammatory drugs) , as well as with concomitant therapy with drugs that may increase the tendency to bleeding, and in patients with a history of bleeding.

Phenomena similar in symptoms to serotonin syndrome or neuroleptic malignant syndrome

In rare cases, the development of serotonin syndrome or neuroleptic malignant syndrome associated with fluoxetine has been reported, especially when used together with other serotonergic drugs (including those containing L-tryptophan) and/or antipsychotics. Because these syndromes can lead to life-threatening conditions, fluoxetine therapy should be discontinued if a combination of symptoms such as pyrexia, rigidity, myoclonus, autonomic nervous system disorders, mental status changes including confusion, irritability, extreme agitation with possible development of delirium and coma occur. , and prescribe the necessary symptomatic therapy.

All patients taking antidepressants for any indication should be closely monitored for signs of clinical worsening, suicidal ideation, and unusual behavioral changes, especially during the first months of therapy or during dose changes (increases or decreases).

Special patient groups

◊ Patients with kidney problems

No special instructions

◊ Patients with liver disease

Reduce the dose - either take it less often, or reduce the dose by half [1].

◊ Patients with heart disease

Safe. Useful in recovery after a heart attack [1].

◊ Elderly patients

Lower doses are recommended for older patients

◊ Children and teenagers

Recommended for the treatment of depression and OCD
It is necessary to regularly and personally check the patient's condition, especially in the first weeks of treatment.
Adult doses are suitable for adolescents.
Inform adults about the risks.
Growth may be slowed in children taking fluoxetine [1].

◊ Pregnant women

There have been no adequate studies in pregnant women [1].
Not recommended for pregnant women, especially in the first trimester
All risks should be weighed and compared
Bleeding can be expected during childbirth

◊ Breastfeeding

The medicine passes into breast milk.
If the infant shows signs of irritation or sedation, discontinue feeding or fluoxetine
However, treatment after childbirth may be necessary, so the risks should be weighed.

The Prozac generation. How they hid the truth about antidepressants from us

Today there is a widespread version that depression is the result of biochemical disorders of the brain. In fact, this is just one of the hypotheses, which is so often replicated in the scientific community that it has come to be perceived as a proven truth.

This happened because psychiatry had no weight in medical science for a long time and, as a rule, was associated with Hippocrates’ theory of four types of temperament and phrenology (the pseudoscience of the connection between the psyche and the shape of the skull). Freud's psychoanalytic theory was not convincing for doctors either. Under these conditions, the hypothesis that mental illness is a consequence of organic disorders of the brain sounded very attractive. This version began to be discussed most often as the main one, but no significant studies confirming it have appeared.

One of the first drugs that “capitalized” the hypothesis of mental illness as a result of biochemical disorders of the brain was Prozac (fluoxetine). The drug appeared in American pharmacies 30 years ago, and we still don’t know how it works or whether it is truly effective in treating depression.

Psychiatrists, who benefit from arguing that depression is a brain disease and not a mental illness, insist on drug treatment. Left behind are various social factors that can also provoke depression: isolation, poverty, tragic events in life and much more. Psychotherapy as a method of treatment is secondary to pills. This distorts not only our understanding of depression, but even our experience of it.

Today, different types of depressive disorders are described*. For example, major depressive disorder, drug-induced depressive disorder, organic mood disorders arising as a consequence of an organic disease. They all differ in etiology and duration, but the symptoms described are generally the same. Patients with different depressive conditions are treated with the same medications, although there is no talk of identical disturbances in the biochemical processes of the brain.

In the 1950s and 1970s, you could buy quite dangerous drugs in American pharmacies to treat depression. Even a slight overdose of these drugs - Butisol (barbiturate) and Valium (diazepam) - could be fatal, which scared off many buyers. The appearance of Prozac on the market changed the situation greatly, because it was a new generation antidepressant - safer and with fewer unpleasant side effects.

The antidepressants available today work more or less the same way. So says Anthony Rothschild, professor of psychiatry at the University of Massachusetts Medical School. Moreover, over the three decades of Prozac's use in the treatment of depression, the selection of antidepressants in pharmacies has grown significantly. However, nothing more effective than imipramine, the main drug among tricyclic antidepressants, has ever been created.

All this time, nothing stopped manufacturers of antidepressants from claiming that depression was a brain disorder that could be corrected with pills: both Paroxetine and Zoloft (sertraline) were sold as “chemical balance-restoring” drugs. Meanwhile, there are still no convincing, scientifically proven versions of the causes of depression.

According to modern research, in 37 percent of cases, depression is inherited , meaning genetics and biology obviously play a significant role. But since neuroscientists still have no precise way to determine what brain function is considered “normal” and what is not, some of the hypotheses cannot be tested.

If the cause of depression was a serotonin imbalance, SSRIs would work instantly rather than require a long dosing cycle**. In addition, a decrease in serotonin levels in the brain should provoke depression, but research shows that this is not the case. This doesn't mean that antidepressants aimed at restoring serotonin levels don't work. But we don't know whether they ultimately affect the root cause of depression or just combat its consequences.

Our ideas about diseases and their nature influence their course. For example, the symptoms of anorexia in Hong Kong patients changed as people in the region became more aware of how the disease occurs in Western countries. Perhaps our current understanding of depression and the medical approach lead to the fact that the disease affects more people: psychiatry calls even those conditions that were previously considered stress or emotional decline mental illness.

According to this study, the placebo effect in treating depression is almost as good as taking antidepressants. The difference is so small that it practically does not affect the clinical picture. Study author Irwin Kirsch, director of the Placebo Research Program at Harvard Medical School, is a strong proponent of non-drug treatments for depression. Research shows that the pills combined with psychotherapy are effective in the short term, but patients who undergo psychotherapy without taking the medication feel better over a longer period of time and have a significantly lower relapse rate. Kirsch, of course, is full of opponents who, on the contrary, are convinced that drugs are necessary.

The truth, as often happens, is somewhere in the middle: patients with severe depression who do not have the strength to go to psychotherapy should definitely be prescribed medications. Those who are able to undergo psychotherapy should definitely do so, especially since drug treatment does not help all patients. Cognitive-behavioral psychotherapy has also proven itself to be effective in the treatment of depression, which will cost more than drugs, but the effect of which will be more sustainable.

Depression has become a global epidemic, affecting one in four people in the world today. It is obvious that the reasons are not only in biology, but also around us: poverty, unemployment, sexual violence - it is impossible to stop the epidemic if you do not fight all the reasons, many of which - alas - cannot be defeated with pills.

In DSM-5 - the 5th edition of the American Diagnostic Manual of Mental Disorders

** SSRIs - Selective serotonin reuptake inhibitors - a group of third generation antidepressants

Side effects and other risks

◊ Mechanism of side effects

Side effects are caused by an increase in serotonin. Most side effects occur immediately after starting treatment and go away over time, while the therapeutic effects increase over time. At the beginning of the course, agitation, activation and anxiety may appear

◊ Side effects

Gastroenterological (reduced appetite, nausea, diarrhea, constipation)
Insomnia, sedation, agitation, tremor
Sweating
Dangerous side effects: seizures, mania, suicidal ideation
Weight gain: very rare
Sedation: very rare
Sexual dysfunction: yes

◊What to do about side effects

Wait
If fluoxetine activates, take in the morning to avoid insomnia
Reduce dose to 10 mg, when side effects go away, increase to 20 mg
Side effects may appear briefly as the dose is increased
Benzodazepines are recommended for anxious patients, especially at the beginning of treatment [1].

◊ Long-term use

Safely

◊Addiction

No.

◊ Overdose

Very rare cases of fatal overdoses.
In combination with alcohol – respiratory depression, ataxia, sedation

PROZAC

Interaction

Fluoxetine and its main metabolite norfluoxetine have long half-lives, which must be taken into account when combining fluoxetine with other drugs, as well as when replacing it with another antidepressant. Fluoxetine has a high affinity for plasma proteins, so the combination of fluoxetine with other drugs, which also significantly bind to plasma proteins, can lead to changes in their concentrations. Monoamine oxidase inhibitors (MAOIs). The use of fluoxetine in combination with MAO-A is not recommended (see section “Contraindications”). When using fluoxetine in combination with MAO-B (selegiline), special precautions must be taken: there is a risk of developing serotonin syndrome. Close clinical monitoring is recommended.Remedies. affecting the central nervous system. Changes in the concentrations of phenytoin, carbamazepine, haloperidol, clozapine, imipramine and desipramine in the blood were detected when combined with fluoxetine. In some cases, manifestations of intoxication were noted. Increasing the dose of these drugs when used simultaneously with fluoxetine should be done with caution and under monitoring of the dynamics of the clinical condition. Serotonergic drugs Concomitant use of serotonergic drugs (for example, SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs), tramadol and triptans) increases the likelihood of developing serotonin syndrome. Simultaneous use of triptans also increases the likelihood of developing coronary vasoconstriction and arterial hypertension. Benzodiazepines. With the simultaneous use of fluoxetine and benzodiazepines, the half-life of the latter may increase. When diazepam or alprazolam was taken together with fluoxetine, an increase in the concentration of benzodiazepine in the blood and an increase in its sedative effect were observed. Lithium and tryptophan .
There are known cases of the development of serotonin syndrome while taking SSRIs and lithium or tryptophan, and therefore the simultaneous administration of fluoxetine with these drugs should be carried out with caution.
When taking fluoxetine and lithium concomitantly, more frequent and careful monitoring of the clinical condition is necessary. Medicines metabolized with the participation of the CYP2D6 isoenzyme (propafenone, carbamazepine, tricyclic antidepressants).
It should be taken into account that the metabolism of fluoxetine (as well as tricyclic antidepressants, as well as selective serotonergic antidepressants) is carried out with the participation of the CYP2D6 isoenzyme of the liver cytochrome system. Simultaneous use of drugs, the main route of biotransformation of which is metabolism with the participation of the CYP2D6 isoenzyme, and having a small range of therapeutic doses (such as propafenone, carbamazepine, tricyclic antidepressants) should be carried out using minimal therapeutic doses. The above also applies if less than 5 weeks have passed since stopping fluoxetine.

Indirect anticoagulants and other
drugs that affect the blood coagulation system (warfarin, non-steroidal anti-inflammatory drugs, aetyl salsyl acid).
There is a known change in the anticoagulant effect (according to laboratory parameters and/or clinical manifestations) without any general characteristic trend, but with the likelihood of increased bleeding when taking fluoxetine and oral anticoagulants simultaneously. The functional state of the blood coagulation system in patients receiving warfarin should be carefully monitored when prescribing and discontinuing fluoxetine.

Drugs. metabolized with the participation of the CYP3A4 isoenzyme. In an in vivo interaction study using fluoxetine in combination with single doses of terfenadine (a CYP3A4 substrate), no increase in plasma concentrations of terfenadine was observed.

In addition, in vitro studies have shown that the inhibitory activity of ketoconazole, a potent inhibitor of the CYP3A4 isoenzyme, is at least 100 times greater than the activity of fluoxetine or norfluoxetine in inhibiting the metabolism of several substrates of this enzyme, including astemizole, cisapride and midazolam. Such studies indicate that the degree of inhibition of CYP3A4 activity by fluoxetine is of little clinical significance.

Electroconvulsive therapy (ECT). There have been rare reports of increased seizure duration in patients taking fluoxetine and receiving ECT, and caution is advised.

Alcohol. In experimental studies, fluoxetine did not increase blood alcohol concentrations or enhance the effects of alcohol. However, simultaneous use of SSRIs and alcohol is not recommended.

Facilities. containing St. John's wort. As with other SSRIs, a pharmacodynamic interaction may develop between fluoxetine and products containing St. John's wort, which may lead to increased undesirable effects.

Tamoxifen. Fluoxetine, as a strong inhibitor of the CYP2D6 isoenzyme, when used simultaneously, reduces the concentration of the active metabolite of tamoxifen (endoxifen) in the blood plasma by 65-75%. Therefore, fluoxetine should be avoided during tamoxifen therapy.