There are individual differences in the efficacy and adverse effects of anxiety disorder treatment medications, and such differences are difficult to predict prior to treatment. The choice of medication depends on the patient’s physical condition, type of illness and adverse drug reactions, and the physician’s personal experience is also very important. The following is a description of the characteristics of several types of commonly used therapeutic drugs.
I. Antidepressants
(A) Antidepressant action characteristics for panic disorder
Many randomized controlled trials have supported the effectiveness of selective 5-HT reuptake inhibitors (SSRIs) for panic disorder. The American Psychiatric Association (APA) practical guidelines for panic disorder recommend SSRIs as the drug of choice for the treatment of panic disorder based on the good tolerability and safety of SSRIs compared to older antidepressants such as tricyclic antidepressants (TCAs). Among them, paroxetine was the first SSRI approved by the FDA for the treatment of panic disorder, and numerous randomized controlled trials have demonstrated the safety and efficacy of the drug, including the later approved paroxetine controlled-release tablets. Sertraline, another SSRI approved by the FDA for the treatment of panic disorder, also has substantial evidence of safety and efficacy and has been shown to be no less effective than fluoxetine. Other SSRIs such as fluvoxamine, citalopram, and escitalopram have also been shown to be safe and effective for panic disorder in multiple randomized controlled trials. Although some SSRIs have been approved by the FDA for the treatment of panic disorder, there are others that have not. Our experience is that these classes of medications have comparable efficacy for panic disorder. Our selection criteria are based on the following considerations: for patients who have been previously treated with an SSRI with good efficacy, this drug may be the first choice for that patient; for patients who have had some intolerable side effects with a drug, this drug should not be used; because of the long treatment period for this disorder, the price of the drug is also a factor to be considered when prescribing.
Venlafaxine extended-release doses of 75-225 mg in the dual re-uptake inhibitors of 5-HT and norepinephrine (NE) are effective in the treatment of panic disorder and have been approved by the FDA. Mipramine and other tricyclic antidepressants as well as heterocyclic antidepressants (e.g., desipramine, clomipramine) are also effective in the treatment of panic disorder. However, the common side effects of these drugs and the fact that patients with panic disorder seem to be more sensitive to the side effects of these drugs have led to their limited use.
(ii) Characteristics of antidepressant action in the treatment of generalized anxiety disorder
Over the past decade or so, SSRIs have also become the first-line treatment for generalized anxiety disorder. SSRIs first reduce psychogenic anxiety including apprehension and obsessions in patients with generalized anxiety disorder, have no effect on muscle tension or autonomic disorder symptoms, and do not improve somatic symptoms as much as benzodiazepines. However, it has been clinically observed that with improvement in psychogenic anxiety, most patients can feel improvement in somatic symptoms. There is substantial evidence that the SSRIs citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, 5-HT and noradrenaline (NE) reuptake inhibitors (SNRIs) venlafaxine are all effective in generalized anxiety disorder.
Tricyclic antidepressants (TCAs), including clomipramine, doxepin, amitriptyline, and mipramine, are 5-HT and norepinephrine (NE) reuptake inhibitors. Some studies have shown that mipramine has a better anxiolytic effect than benzodiazepines and improves mainly psychogenic anxiety. It should be noted that TCAs with antihistamine effects can reduce alertness; their anticholinergic effects can cause dry mouth, constipation, difficulty urinating, rapid heartbeat, increased intraocular pressure, difficulty with eye regulation, and cognitive impairment; TCAs have quinidine-like effects on myocardial and cardiac conduction, and they are more toxic than SSRIs. As a result, they are now less commonly used in the treatment of anxiety disorders. However, in patients with irritable bowel syndrome, their anticholinergic effects can relieve abdominal pain and discomfort by slowing intestinal motility. In addition, TCAs are effective and inexpensive for patients with migraine.
Our clinical experience is that SSRIs have similar efficacy, except that fluoxetine is inconvenient to adjust the dose because of its long half-life; TCAs, SSRIs, and SNRIs may aggravate anxiety symptoms at the beginning of treatment and need to be avoided by lowering the starting dose or adding anxiolytics. SSRIs may cause headache, diarrhea, nausea, sexual dysfunction, and may also affect the hepatic cytochrome P450 enzyme system; SSRIs must be tapered during the withdrawal phase to avoid self-limiting discomfort withdrawal symptoms; venlafaxine and duloxetine in SNRIs may also cause nausea, dizziness, and sexual dysfunction and affect cytochrome enzymes, and venlafaxine may cause increased blood pressure; antidepressants should be used at lower doses for generalized anxiety disorder than for panic disorder; many patients with stress-induced Many patients with generalized anxiety disorder due to stress achieve complete remission within a few weeks or months of treatment, often without long-term medication, and antidepressants are useful for those with severe and persistent symptoms of mental anxiety.
In addition, trazodone, a 5-HT reuptake inhibitor and 5-HT2 receptor antagonist, is effective in the treatment of generalized anxiety disorder. Because of its better sedative-hypnotic effect, it is often used as a sedative in combination with antidepressants without sedative effects at night. Mirtazapine, an antidepressant with a specific mechanism of action, was shown to be effective in a study of generalized anxiety disorder with depression co-morbidity. It does not aggravate anxiety at the beginning of treatment and improves sleep, but is less sedating. It is not recommended for patients with hyperlipidemia and diabetes because of its appetite and weight increasing effects.
Second, benzodiazepines
In the past, benzodiazepines were the most commonly used drugs for the treatment of anxiety disorders. Today, these drugs still have an important place in the treatment of anxiety disorders. Benzodiazepines have sedation, muscle relaxation, reduce anxiety, improve the role of seizure threshold; also can significantly reduce alertness, induce relaxation, high doses will produce drowsiness. This class of drugs has little efficacy on psychiatric symptoms; common clinical doses can only mildly reduce apprehension, meditation, and interpersonal hypersensitivity tendencies.
Benzodiazepines have a good rapid anxiolytic effect, and longer-term and regular use produces tolerance to the sedative effects, but there is little evidence of tolerance to their anxiolytic effects. Patients may continue to request dose increases in search of euphoria rather than anxiety reduction. Because the development of tolerance quickly progresses to euphoria, patients will then seek high doses of the drug.
There are a number of clinically available varieties that differ minimally in efficacy, with the difference being primarily in the rate of absorption and half-life of the drug in the body. Fast-absorbing drugs such as lorazepam or alprazolam can quickly relieve anxiety, but because they tend to produce a “high,” they have a greater propensity for addiction than slower-absorbing drugs such as oxazepam. When administered chronically, drugs with long half-lives, such as diazepam and fludiazepam, have a greater efficacy advantage because their pharmacological effects are more stable than those of drugs with shorter half-lives. However, due to low clearance, they may accumulate in the body and cause excessive sedation, especially in the elderly and in patients with hepatic or renal insufficiency. Benzodiazepines can be shared with most drugs, but increase the effects of alcohol and sedatives.
The biggest disadvantage of benzodiazepines is the tendency to become addicted. Therapeutic doses alone can cause somatic dependence (e.g., inability to reduce the dose). The severity of withdrawal symptoms depends on the dose, duration of application, patient personality, and genetic factors. Patients with a history of substance abuse and a positive family history of chronic alcoholism are more likely to develop dependence. Withdrawal symptoms from benzodiazepines are similar to anxiety symptoms, and it is clinically difficult to distinguish whether withdrawal symptoms or anxiety symptoms are reproduced, or whether they coexist. Because withdrawal symptoms disappear within 2 weeks, the patient’s underlying anxiety level cannot be determined until 3 to 4 weeks after the drug is reduced or discontinued.
In general, benzodiazepines can be used either singly or regularly. They are particularly indicated for patients with somatic manifestations of anxiety because of their ability to significantly reduce levels of alertness and autonomic nervous system symptoms. Compared to other sedatives and anxiolytics, they are relatively safe even when ingested in excess. Their biggest drawback is addictive properties.
Eollister 1979 recommended the use of benzodiazepines, which can be used as a reference for clinical use. Specifically as follows: 2h before bedtime to take a drug, if the patient before going to bed slightly sleepy, or sleep more comfortable than usual, or wake up later the next morning, or wake up still some not enough sleep and less awake feeling, this dose is appropriate (Eollister called semi-hypnotic amount). Start treatment with a small dose, such as Valium 2mg, and increase the dose every night up to 20mg until the semi-hypnotic amount is determined. The dose is usually determined over 3 to 5 nights. Formal treatment is then administered. The plasma concentration half-life of these drugs are long (12-48h), so the traditional three daily doses are not necessary, and two daily doses are sufficient. Each dose is half a hypnotic amount, one in the morning and one in the evening.
Third, other types of drugs
Some studies have shown that buspirone is more effective than placebo for generalized anxiety disorder, but not as effective as venlafaxine; it is ineffective in the treatment of panic disorder. Compared with benzodiazepines, buspirone appears to have better effects on psychiatric symptoms than on somatic symptoms, and it also has better treatment effects on depressive symptoms that often co-morbid with anxiety disorders. Buspirone is non-addictive and has mild side effects, with nausea and headache being the most common; it should be taken regularly for at least 2 weeks to be fully effective.
Antihistamines cause drowsiness and sedation and are less anxiolytic than benzodiazepines, and may cause significant side effects at effective therapeutic doses. However, they are non-addictive and fast-acting, and can be given intermittently or regularly, especially for patients with a propensity for substance abuse.
Atypical antipsychotics such as olanzapine, quetiapine, and risperidone are also often used to reduce anxiety. However, the benefits need to be weighed against the risks when using these drugs, and they are generally used only for the small number of people with generalized anxiety disorder who have responded well to their treatment.
Beta-adrenergic blockers do not directly affect psychogenic anxiety, but they can reduce the cardiac response due to anxiety by lowering the heart rate and reducing, among other things, muscle tremors, which can lead to psychological calm in some patients. These drugs are fast-acting and can be used temporarily or regularly.
Many anticonvulsants such as valproate, gabapentin, and etiracetam have been suggested as potentially useful in the treatment of anxiety disorders, but evidence of their effectiveness is insufficient.