Although the various antidepressants do not vary much, each one has its unique advantages and there is always one that is most suitable for some specific patients. Most patients encountered in clinical practice are not simply depressed, but may also have concomitant chronic pain, sexual dysfunction, anxiety, chronic fatigue syndrome, fibromyalgia, severe insomnia, advanced age, diabetes, and heart disease.
Which antidepressants are best for patients with depression with these symptoms? Suppose you were to meet such patients, how would you choose antidepressants? Do you really have a good idea? Dr. Shul from the Department of Psychiatry at Cleveland Medical Center has answered these questions in the Cleveland Clinic Journal of Medicine (CCJM).
The following article, no matter how many stars are marked, cannot match its importance. It is recommended that every clinician collect it, because there are so many patients with depression, and it is not guaranteed that the patient you have now is accompanied by depression.
I. Basic laboratory tests
Before starting antidepressant treatment, it is recommended to obtain a set of laboratory test results at baseline in order to exclude somatic causes of depression or to better guide the application of antidepressants. (For example, duloxetine is not recommended for patients with hepatic insufficiency.)
The following tests are recommended: blood counts, metabolomic tests, and measurement of TSH levels. Sometimes an electrocardiogram is also recommended because some antidepressants can cause a prolonged QT interval in patients or a prolonged QT interval due to increased blood levels from the combination of other drugs.
Precautions in treatment
Depending on the mechanism of action, antidepressants are often divided into the following four categories.
SSRI, SNRI, TCA and MAOI. Studies have shown that the difference in efficacy of different drugs with the same mechanism is small.
1. Medication principles
When starting antidepressant medication, follow the medication principles: start with a low dose and add the medication slowly. It is generally recommended that the starting dose be half of the regular dose, and if the patient can tolerate it, gradually increase the dose every 2 weeks. For example, if you plan to use fluoxetine, the initial dose is 10 mg, and then the dose is gradually increased according to the patient’s tolerance and efficacy.
In other words, even for the same drug, its efficacy and side effects may be different due to individual differences, but the same is that the side effects can be minimized according to the principles of antidepressant drug application, and also, the doctor needs to have an antidepressant drug treatment plan.
2.The problem of side effects
As for the side effects of antidepressants, in fact, everything has its two sides, and so do antidepressants, which can also lead to side effects when they play a therapeutic role, but when choosing antidepressants, according to their mechanism, it is generally possible to predict their side effects, which are often short-lived and have a better prognosis, so that patients can be informed and reassured.
We will discuss the side effects of antidepressants more specifically in future articles, so please pay more attention to the articles in the WeChat public number “Spiritual Time” in general.
3. Evaluate the efficacy of treatment
If the patient does not respond well after 4-6 weeks of medication, it is time to consider changing the medication. If a patient has been on an SSRI, he or she may choose another SSRI or SNRI for the next dose. However, if neither SSRI has worked, choose an SNRI.
When switching medications, it is necessary to gradually reduce the dosage to avoid withdrawal reactions and to reduce potential adverse effects caused by switching medications, such as CYP450 interactions, 5-HT syndrome, and hypertensive crisis (when switching to MAOI).
4. Pay attention to drug interactions
All SSRI and SNRI drugs are metabolized by the liver, and when these drugs are used in combination, they can affect their metabolic rate by inhibiting CYP450, which can cause an increase in blood concentration or even serious adverse reactions.
For TCA drugs, if you are concerned about toxicity, you can have a blood level test. If TCA needs to be used in combination with SSRI or SNRI, it is important to be alert to drug interactions, as the blood concentration of TCA is very high and may lead to prolonged QT interval.
Specific medications
1. Treatment of patients with simple depression
For patients with simple depression without obvious physical problems, SSRIs are usually the first choice for antidepressants.
In general, depressive symptoms will improve within 2 weeks, and the best response can be obtained within 4-6 weeks of treatment.
2. With chronic pain
Depression is often associated with pain, and a vicious cycle can form between the two. When patients have both depressive symptoms and pain, SNRIs and TCAs are generally preferred.
Some SNRIs, such as duloxetine and milnacipran, have been approved for specific chronic pain patients, such as fibromyalgia. Sometimes SNRIs are often used externally as indications for the treatment of some other chronic pain, such as headache and neuropathic pain.
TCAs, such as amitriptyline, nortriptyline, and doxorubicin, are also commonly used in patients with chronic pain. Like SNRIs, they inhibit the reuptake of 5-HT and norepinephrine and are often used for neuropathic pain, migraine, interstitial cystitis, or other pain outside of their indications.
For the TCAs and SNRIs class of drugs, the effective dose ranges for the treatment of chronic pain overlap with those for the treatment of depression. However, the starting dosage of TCAs is lower for patients with chronic pain who do not have depression. For both drugs when used in patients with depression with chronic pain, it is recommended to start with a low dose and slowly increase the dose until an effective dose is achieved.
In addition, SNRIs are generally preferred. Simply because TCAs are more toxic and can cause tachycardia, postural hypotension, ECG abnormalities, drowsiness, etc. More importantly, overdose can be fatal and some patients use them as a suicide tool.
3. With sexual dysfunction
For patients treated with antidepressants, sexual dysfunction is often reported to physicians, commonly with delayed orgasm or decreased libido. Generally, patients taking SSRIs and SNRIs complain the most, but of course, TCAs and MAOIs also have problems related to sexual dysfunction.
In addition, the presence of impotence and abnormal persistent penile erection is associated with specific antidepressants; for example, trazodone can cause abnormal persistent penile erection, and even with low doses of trazodone, for men, the side effects need to be noted.
It is important to note that switching to another antidepressant for the same class is unlikely to improve the patient’s sexual dysfunction because the mechanisms that cause sexual dysfunction are similar. For sexual dysfunction on SSRIs, switching to bupropion or mirtazapine may be useful because bupropion acts primarily on dopamine and norepinephrine receptors and mirtazapine acts primarily on 5-hydroxytryptamine and norepinephrine receptors.
For sexual dysfunction due to antidepressants, there are complementary treatments such as anticholinergics, yohimbine (forbidden in combination with MAOIs), buspirone, and drugs that act on NO receptors, such as sildenafil and tadalafil, which are practical, but often ineffective.
If these are not resolved, if possible, reducing the dose of antidepressants may work.
4, accompanied by anxiety
Many antidepressants have the same indications for anxiety disorders, but other antidepressants still treat anxiety disorders with indications that are foreign. In clinical practice, we can often find that depression and anxiety often appear at the same time, you can use a drug to address both depression and anxiety. Overall, SSRIs and SNRIs act as antidepressants at relatively low doses; they act as anxiolytics at high doses, especially for OCD.
First-line treatment is an SSRI or SNRI. most anxiety disorder coping classes, but there are some more specific recommendations. SSRIs are best used for panic disorder, generalized anxiety disorder, social anxiety disorder, post-traumatic stress disorder, and obsessive-compulsive disorder.
For patients with concomitant anxiety, often the first-line medication of choice will be SSRIs or SNRIs, capable of handling most anxiety disorders. But when you think about it, each drug has a more specific use. SSRIs have been studied more for panic disorder, generalized anxiety disorder, social phobia, PTSD, and OCD.
Fluoxetine, citalopram, escitalopram and sertraline are also effective in patients with depression with generalized anxiety disorder. Patients with panic disorder appear to respond better to SSRIs. SNRIs have also been used to evaluate the treatment of generalized anxiety disorder and may be effective for other conditions as well.
In addition, mirtazapine (outside of the indications) and TCAs may also be used to treat anxiety disorders. Clomipramine has also been used to treat obsessive-compulsive disorder. These medications are particularly indicated for the treatment of nocturnal anxiety, as they can assist with sleep. It is important to note that mirtazapine is more effective at higher doses when used as an anxiolytic.
MAOIs are often not recommended because of dietary and medication factors, but may be beneficial for some patients with specific anxiety disorders that are refractory to treatment.
Bupropion is more activating than other antidepressants and is therefore often avoided in patients with anxiety disorders; however, some findings suggest that this is not absolute and that significant improvement may be obtained with bupropion if the anxiety is secondary to depression.
It is still important to always remember the principles of dosing: low starting doses, slow additions, and patients who may feel more anxious or nervous during the first week of treatment need to be informed in advance by our physicians, otherwise it will make them more anxious and reduce compliance. In addition, the use of benzodiazepines, such as clonazepam, can also be used as an adjunct, which may make the patient more tolerant.
5. With chronic fatigue syndrome or fibromyalgia
Increasing recognition of chronic fatigue syndrome and fibromyalgia is a strategy for aggressive treatment of these disorders. In addition, for depressed patients with these two disorders, treatment with specific antidepressants, also known as SNRIs, may be beneficial for such patients.
For the treatment of fibromyalgia, there are still many research data. Both duloxetine and milnacipran are approved by the FDA for the treatment of fibromyalgia. In addition, venlafaxine is also used for the treatment of fibromyalgia as an exotic indication.
TCAs have also been used successfully in the treatment of fibromyalgia, but their side effects have limited their use in the clinic. Recently, a study from Spain has shown that MAOIs can also be used to treat fibromyalgia, but the quality of the study needs to be improved.
Some of the current data for SSRIs, SNRIs, and MAOIs for the treatment of chronic fatigue syndrome are conflicting and need to be further investigated.
6, with insomnia
Insomnia can be both a symptom of depression and a side effect caused by specific antidepressants. SSRIs and SNRIs can disrupt the sleep patterns of some patients by shortening the rapid eye movement (REM) cycle.
For patients with severe insomnia, it is recommended that patients take antidepressants in the morning if they find that their sleep has worsened when they start antidepressant medication. For any patient taking antidepressants, the doctor can tell the patient, “If you are taking an antidepressant and it makes you feel sleepy, then take it at night; if it is making you insomniac, then take it in the morning. It is worth noting that a recent study from South Africa showed that escitalopram can improve sleep.
If the above measures don’t solve the problem, don’t worry, there are other treatment options. For example, mirtazapine, especially at doses of 15 mg or 30 mg, can be an adjunct to treat depression and insomnia, with the caveat that its sleep-assisting effects may be diminished when mirtazapine is at 45 mg.
In addition, lower doses of TCAs, especially doxepin, maprotiline (which is technically a tetracyclic antidepressant), amitriptyline, and norethindrone, also have good adjunctive effects on sleep, and these drugs may be used as adjuncts to other antidepressants to improve sleep and mood. It is important to note that TCAs also shorten the REM cycle.
With the previously mentioned SSRIs and SNRIs, it is important to be aware of drug-drug interactions, especially when discontinuing these medications, and it is worth being alert to the fact that patients may experience rebound symptoms, i.e., experience more vivid images of dreams.
In the case of MAOIs, insomnia may be worsened because this class of drugs suppresses REM.
Trazodone can be an effective, non-addictive sleep aid at low doses (25-250 mg). When it is used as an antidepressant, higher doses (300-400 mg) are usually required, but at this point, its sedative effects should not be ignored. It should also be noted that the drug has the potential to cause abnormal penile erections in men.
7, elderly patients
When treating elderly patients with depression, there are many issues to consider when administering medication. For example, SSRIs are more likely to cause bradycardia when taken by older patients; TCAs produce more cardiac toxicities and can also affect cognitive function, whereas SSRIs, bupropion and SNRIs rarely cause changes in cognitive function.
Escitalopram and duloxetine are commonly recommended for elderly depressed patients, but it is important to note that a study from the Netherlands showed that SSRIs increased the risk of falls in elderly depressed patients with coexisting dementia.
In addition, when using TCAs and paroxetine, attention needs to be paid to constipation in elderly patients, as it not only affects quality of life and compliance, but may also lead to bowel obstruction.
Also, mirtazapine is commonly used in elderly patients for a number of reasons: not only does the drug reduce depression and anxiety, it also increases appetite and weight, helps with nausea, and aids in sleep, and aren’t these supposed side effects just what elderly patients need? But for younger patients, weight gain and sleeping more may not be a good thing.
As we continue to age, sleep cycles change, which can lead to a decrease in satisfaction with sleep. In addition, depression usually further affects sleep, so optimizing sleep is key for older patients with sleep problems. Studies suggest that mirtazapine is effective for elderly patients with dementia.
8. With diabetes
For psychiatric drugs, most of them will make patients gain weight, which certainly can’t hurt for diabetic patients. Some antidepressants can significantly increase the patient’s weight, for this group of people, it is not recommended as a first-line medication. In general, these drugs have strong antihistamine properties, such as paroxetine and TCAs, which can cause constipation and potentially worsen gastroparesis.
As you know, mirtazapine and MAOIs can cause weight gain in patients.
Of all antidepressants, bupropion and nefazodone are the ones that least affect patient weight. It should be noted, however, that nefazodone is being withdrawn from clinical use because of the potential for fulminant liver failure in rare cases, but it remains an appropriate choice for depressed and anxious patients who are using other antidepressants that cause significant weight gain.
SSRIs and MAOIs may or may not affect glucose metabolism, and data from some studies also suggest that SNRIs may impair glucose metabolic processes.
9. Concomitant heart disease
Many patients with depression also have coexisting heart conditions. In particular, many patients suffer from depression after a myocardial infarction, and it is essential to deal with depression at this time, not thinking that depression is only a mental illness, but that it also increases the risk of another myocardial infarction.
However, managing depressed patients with heart disease can be difficult. It is recommended that an electrocardiogram be done before starting antidepressant medication to serve as baseline data for later comparison.
Tricyclic and tetracyclic antidepressants increase the risk of prolonged QT intervals and ventricular arrhythmias, so they should be avoided in patients with these two symptoms. In addition, these two classes of drugs significantly increase the pulse rate of patients. It is important to note that the anticholinergic effects of these drugs can cause tachycardia and increase the risk of angina pectoris and myocardial infarction in patients.
In February 2013, the FDA issued a warning about possible arrhythmias in adult patients using more than 40 mg of citalopram, but some studies have shown that citalopram is effective in patients with depression who also have heart disease, but there is no indication that daily doses above 40 mg increase its efficacy, so it is recommended that you follow the black box warning issued by the FDA.
TCAs and MAOIs can cause upright hypotension. On the other hand, in patients taking MAOIs, there is also a need to be alert for hypertensive crisis when patients consume foods containing high levels of tyramine.
All this talk seems to miss the point of which antidepressant medications can be safely used in depressed patients with heart disease. So here come these drugs.
Sertraline has been shown to be safe for depressed patients with congestive heart failure and coronary artery disease, but SSRIs are generally safe. Fluoxetine is effective for depression in the presence of myocardial infarction. Mirtazapine is also safe and effective in patients with cardiac disease. For upright hypotension, nefazodone, mirtazapine, bupropion, SNRIs, and SSRIs appear to have little or no effect.
Conclusion.
Duloxetine as an SNRI is efficacious in patients with depression with anxiety and somatic symptoms; the question is, how safe and well tolerated is duloxetine in the clinic?