Panic disorder with or without agoraphobia: treatment

If a panic disorder is diagnosed (with or without agoraphobia) and somatic or neurological pathologies are excluded, SSRIs are usually used as the drugs of choice, but in some situations an exception is made.

In most patients with panic disorder, especially with comorbid major depression or with a history of substance misuse, treatment should begin with SSRIs. Initially, patients with panic disorder are prescribed very low doses: 5-10 mg fluoxetine, 25 mg fluvoxamine, 25 mg sertraline or 10 mg paroxetine. The patient should be fully informed about the side effects of SSRIs, special attention should be given to a possible increase in excitability. It should also mention the side effects in the sexual sphere and the risk of developing a manic condition. The doctor should pay attention to concomitant therapy. Initially, SSRIs are prescribed in the morning, given the possibility of excitation. But some patients, on the contrary, experience drowsiness - in this case, it is advisable to transfer the drug to the evening.

The dose of SSRIs is increased gradually, usually once a week, carefully observing whether it was due to an increase in the dose of anxiety increase or the increase in panic attacks. After a few weeks, the dose can be increased faster. With increasing anxiety, the dose is reduced or increases more slowly. Control of the concentration of SSRI in the blood in clinical practice is not used, but it may be necessary to monitor the concentration of concomitant drugs, for example, tricyclic antidepressants.

The anxiolytic effect of SSRIs usually manifests itself not earlier than a week after initiation of therapy. The therapeutic effect reaches a maximum in a few weeks or months - depending on the tolerability of the drug and, consequently, the rate of dose build-up. With panic disorder, the same doses are effective as in the case of major depression. The lower limit of effective doses corresponds to 20 mg / day of fluoxetine and paroxetine, 50 mg / day of sertraline, 150 mg / day of fluvoxamine, 40 mg / day of citalopram. The daily dose of most SSRIs can be taken once a day.

Although there is no conclusive data on the benefits of the effectiveness of a given drug, there are a number of factors that influence the choice of the drug in this particular patient. For example, if a patient, along with SSRIs, needs to take other drugs, the choice of SSRIs depends on its effect on cytochrome P450 - avoid the appointment of a drug that, while affecting the metabolism of another agent, can cause complications. In addition, it is necessary to take into account the differences in pharmacokinetic parameters. Thus, "undisciplined" patients prefer to prescribe drugs with a long half-eli- mination period, for example, fluoxetine. If a patient misses taking a drug with a short half-elimination period, then a withdrawal syndrome may develop with a rebound in anxiety. But when taking a drug with a long period of half-elimination these phenomena are rare. But if the patient will need to prescribe other drugs, it is better to choose an SSRI with a shorter half-elimination period. So, because of a long period of life, the concentration of fluoxetine in the blood remains high enough for several weeks after the drug was discontinued. This makes it difficult to prescribe other drugs, especially MAO inhibitors and tricyclic antidepressants, which are often prescribed in cases that are resistant to treatment.

High-potential benzodiazepines are indicated for panic disorder, mainly in two situations. First, benzodiazepines can be a drug of choice in patients who are not dependent on a psychotropic agent and comorbid major depression, when it is necessary to quickly stop the paralyzing patient anxiety (the effect of SSRIs is developing too slowly). But even in the absence of anamnestic indications of the abuse of psychotropic substances, the patient must be informed in detail about the risk of physical dependence. It is because of this risk that benzodiazepines are considered second-line drugs in the treatment of panic disorder. Usually patients are prescribed SSRIs, and benzodiazepines are used only at the initial stage for rapid relief of symptoms.

In addition, the use of benzodiazepines is preferable in patients with a manic condition in the anamnesis. Unlike other treatments for panic disorder, benzodiazepines do not provoke mania and can be used to treat this condition.

Treatment with benzodiazepines, as well as SSRIs, starts with low doses. Clonazepam is usually preferred, in part because of the higher risk of withdrawal syndrome when taking alprazolam. Nevertheless, there are isolated reports that clonazepam often causes an increase in depression than alprazolam. In many patients clonazepam is effective at a dose of 0.25-0.5 mg 2-3 times a day (if necessary, additional intake of the same dose is allowed). With a mildly expressed panic disorder, the effective daily dose usually does not exceed 2 mg. But sometimes to achieve full remission, the dose should be increased to 4 mg / day. Treatment with alprazolam begins with a dose of 0.25-0.5 mg 3 times a day, followed by an increase to 2-6 mg / day. But in some cases, the dose should be increased to 10 mg / day - the maximum recommended dose. Because of the short half-elimination period, alprazolam is prescribed 4 times a day, if necessary, an additional dose is allowed.

With a positive effect, taking the drug should be prolonged for at least 6 months. With the withdrawal of benzodiazepines, abstinence symptoms may occur. In these cases, a slower decrease in doses is recommended for 1-2 months. Abstinence of benzodiazepines can be facilitated by ancillary psychotherapy of a cognitive-behavioral nature. If the patient does not tolerate even a slow dose reduction, then it is recommended to replace the drug with benzodiazepine with a longer half-life or add SSRIs and then try to cancel benzodiazepine. With a good effect, treatment is advisable to continue for a long time. But many patients still prefer to cancel drugs as quickly as possible.

If SSRIs are ineffective, benzodiazepine, a tricyclic antidepressant, or a new mixed serotonin reuptake inhibitor and norepinephrine (for example, venlafaxine) may be used. Before the appointment of a tricyclic antidepressant in patients with somatic diseases, children and the elderly, an ECG is necessary to exclude cardiac conduction disorders. Patients should be warned about the possibility of cholinolytic side effects and orthostatic hypotension. Treatment with venlafaxine, as well as SSRIs, should begin with a low dose, since it can cause a transient increase in anxiety.

In anxiety disorders, tricyclic antidepressants are effective at the same doses as with major depression. Treatment of panic disorder with imipramine starts at a dose of 10 mg 1-2 times a day, then it is increased to 200 mg / day (1.5-3 mg / kg / day). The optimal dose is 2.25 mg / kg / day. As with SSRIs, an increase in the dose of a tricyclic antidepressant at the beginning of treatment is gradual, usually 10 mg 1-2 times a week. The optimal level is imipramine and N-desmethylimipramine in the range of 110-140 ng / ml.

There is insufficient data on optimal doses and blood concentrations of other tricyclic antidepressants in the treatment of panic disorder, and therapy should focus on the doses and concentrations used in the treatment of major depression. The therapeutic concentration in blood for desipramine is 125 ng / ml, for nortriptyline 50-150 ng / ml (this is the only tricyclic antidepressant whose therapeutic range is limited at the top of depression). The starting dose of desipramine is usually 25 mg / day, then it is increased to 150-200 mg / day, in some cases - up to 300 mg / day. Treatment with nortriptyline usually begins with a dose of 10-25 mg / day, and subsequently it is increased to 100-150 mg / day. Most of the somatically healthy adults do not need to monitor the ECG, but in children and the elderly it is necessary to record the ECG before each dose change, given the potential for side effects associated with cardiac conduction disorders.

If the drugs of the first and second series are ineffective, MAO inhibitors can be prescribed. MAO inhibitors are highly effective in panic disorder, but their use is limited by the possibility of serious side effects. One of the main disadvantages in the treatment of MAOI is the need for a break in the intake of drugs ("washing-out" period) between the cancellation of SSRIs and the appointment of an MAO inhibitor. When imposing their action, a serotonin syndrome is possible. After a short-acting SSRI treatment, the break should be at least two weeks, after taking a drug with a long half-life (for example, fluoxetine), a break in drug therapy should last up to two months. Treatment of MAOI usually begins with a low dose (15 mg of phenelzine or 10 mg of tranylcypromine), and then it is increased once or twice a week.

The question of the advisability of monitoring the activity of MAO in platelets in case of major depression is discussed, since the therapeutic effect is achieved only with a significant suppression of the activity of the enzyme. In the treatment of anxiety, the need for this technique arises extremely rarely. In panic disorder, MAOI is usually prescribed 2-3 times a day, with an effective dose of phenelzine 60-75 mg / day (about 1 mg / kg), and tranylcypromine 20-30 mg / day.

If the use of MAOI is undesirable, in the case of resistant cases two antipanic agents are combined that can enhance the effect of each other. For example, to enhance the effect of SSRIs, benzodiazepine or vice versa is added. The combination of tricyclic antidepressants with benzodiazepines is also widely used. The disadvantage of this approach is that the side effects of each drug can also potentiate each other. In addition, there is no conclusive evidence that would confirm the effectiveness of this approach. For most combinations (including for a combination of one drug with psychotherapy), randomized clinical trials have not been conducted that would confirm their advantage over monotherapy. With a combination of medicines, care should be taken avoiding drugs whose interaction can lead to dangerous consequences (eg, SSRIs and MAOIs). In combination therapy, third-line drugs can be used, including anticonvulsants (if there are signs of bipolar disorder) or calcium antagonists.

Although one of these schemes succeeds in most of the patients, a panic disorder often has a chronic or recurrent course, so treatment should be lengthy. After receiving the effect, the patient should continue taking the drugs at a stable dose for at least 6 months. If the patient quickly responded to treatment, then the attempt to cancel the drug within a year is justified. If the patient's condition was stabilized with difficulty, then longer therapy is needed. Practically for all drugs in order to avoid withdrawal syndrome, slow reduction of dose is recommended. According to preliminary data, auxiliary psychotherapy can facilitate the procedure of dose reduction in patients who have been taking this or that remedy for a long time.

[1], [2], [3], [4], [5], [6], [7], [8]