Since the emergence of the first antidepressant promethazine in the 1950s, the research and development of antidepressants has developed rapidly. In the past decade, new antidepressants have been marketed for clinical application. Currently, antidepressants are divided into four categories: tricyclics, tetracyclics, monoamine oxidase inhibitors, and novel antidepressants [1]. The representative drugs of each class are as follows.
(i) Tricyclic antidepressants (TCAs).
TCAs belong to the first generation of monoamine reuptake inhibitors, which not only inhibit 5-hydroxytryptamine (5-HT) and norepinephrine (NA) presynaptic membrane reuptake, but also have anticholinergic effects. The adverse effects of these drugs are mainly from anticholinergic effects, such as dry mouth, constipation, urinary retention, blurred vision and increased intraocular pressure, etc. The most serious is cardiotoxicity, especially in elderly patients, such as postural hypotension, arrhythmia, atrioventricular block, heart failure, myocardial infarction, etc. Clinical drugs include clomipramine (chlorpromazine, anaphylline), amitriptyline (amytriptyline, elavil), promethazine (mipramine), doxepin (doxepin), etc.
(ii) Tetracyclic antidepressants.
(iii) Monoamine oxidase inhibitors (MAOI).
In 1957, Kline used MAOI to treat depression to achieve significant efficacy. Its clinical use includes a few kinds of drugs such as cyclopamine, phenelzine and isocarbohydrazide. However, there are more adverse effects, such as toxic liver injury and hypertensive crisis, and the efficacy is much less than that of the tricyclic drugs that appeared later, so they have now become the second choice of drugs for the treatment of depression.
(iv) new antidepressants.
1, selective 5-HT reuptake inhibitors (SSRI)
SSRI is currently the most new drug development in the class. With a high degree of selectivity for 5-HT, less impact on NA, dopamine (DA), histamine and cholinergic nerves, good oral absorption, higher bioavailability, its adverse effects are less, well tolerated, so patient compliance is better than the previous types of drugs. The drug is suitable for all types of depression and is the main clinical application of antidepressants. Some studies have shown that the combination of SSRI and new antipsychotic drugs has better efficacy in treating depression with delusions.
(1) Fluoxetine
Fluoxetine can selectively depress presynaptic membrane re-uptake of 5-HT, and has less effect on NA re-uptake. Its efficacy is similar to that of TCA, while its anticholinergic effect and cardiovascular side effects are smaller than those of TCA. The oral absorption of fluoxetine is good, the plasma half-life is 24 hours to 72 hours, the dose is 20mg to 40mg, the maximum daily dose is 80mg. the efficacy of this drug for the treatment of depression with cardiovascular symptoms is certain, the tolerability is good, and it is suitable for clinical use.
(2) Paroxetine
Paroxetine exerts its effect by inhibiting 5-HT reuptake in brain neurons and is highly selective. It has low affinity for cholinergic, histamine or epinephrine receptors, and has less anticholinergic and cardiovascular adverse effects than TCA. It has no cognitive or psychomotor impairment in patients. The maximum daily dose for elderly patients should not exceed 40 mg. The dose should be gradually reduced for long-term application and should not be stopped suddenly.
(3) Sertraline
Sertraline is a potent and specific inhibitor of 5-HT reuptake in presynaptic neurons. It has no effect on postsynaptic 5-HT receptors and adrenergic receptors. Blood concentration peaks 6 to 8 hours after dosing, with a plasma half-life of about 26 hours. In addition, the drug increases DA release and is less likely to cause Parkinson’s syndrome, increased prolactin, fatigue and weight gain, and can improve cognition and concentration in patients.
(4) Fluvoxamine
Fluvoxamine selectively inhibits 5-HT reuptake by presynaptic membranes, with weak effects on NA and DA, and is one of the more selective 5-HT reuptake inhibitors known. It has no sedative, excitatory, anticholinergic or antihistamine effects, and has no effect on monoamine oxidase. The plasma half-life is approximately 15 hours and the conventional dose is 100 mg daily at bedtime. Clinical experience shows that it can effectively treat various types of depression.
(5) Citalopram
Citalopram is more selective in blocking 5-HT reuptake and has less effect on other neurotransmitters and their receptors. It does not affect cognition and psychomotor behavior. It is particularly indicated for depression associated with somatic disorders that require a combination of drugs, such as post-stroke depression. Citalopram has a plasma half-life of 33 hours and is administered orally at a dose range of 20 mg to 60 mg daily.
2.Selective norepinephrine reuptake inhibitor (NARI)
NARI can block the reuptake of NA by the presynaptic membrane of the central nervous system, so that the function of the NA system can be balanced, but does not affect the reuptake of 5-HT. It is indicated for endogenous depression, psychogenic depression and menopausal depression.
(1) Maprotiline
Maprotiline is a tetracyclic structure, and is an antidepressant that inhibits the reuptake of NA by the presynaptic membrane. It has strong antidepressant, moderate anticholinergic and sedative and tranquilizing effects, and is suitable for depression with obvious characteristics. The commonly used dose is 75mg to 225mg daily.
(2) Reboxetine
Reboxetine is the first NARI in the full sense of the word, which exerts antidepressant effects by enhancing CNS NA function through inhibition of neuronal presynaptic membrane NA reuptake. There is no or lesser effect on 5-HT transmitters. Pharmacological and physiological tests have shown that the drug has weak anticholinergic activity and little affinity for other receptors in the brain.
(3) Mianserin
Mianserin has a strong blocking effect on NA reuptake and antagonizes presynaptic alpha-receptors, thereby increasing NA release and enhancing the function of the NA system. In addition to its antidepressant effect, it also has sedative and anxiolytic effects. The peak blood concentration is reached 3 hours after a single oral dose, and the average elimination half-life is 32 hours. The initial dose is 30mg~40mg per day, the effective dose is 30mg~90mg per day, taken at bedtime, also can be divided into doses.
3.Selective 5-HT and norepinephrine reuptake inhibitor (SNRI)
SNRI can simultaneously block the re-uptake of 5-HT and NA, and mildly inhibit the uptake of DA, and can be used alternately with TCA for the treatment of depression.
(1) Venlafaxine
The main pharmacological mechanism of venlafaxine is to inhibit the reuptake of 5-HT and NA by presynaptic membrane and enhance the function of central 5-HT and NA neurotransmitters to exert antidepressant effects. Its extended release agent is well absorbed orally, with a relative bioavailability of 96% to 104% and a plasma half-life of about 15 hours. The drug has been approved for marketing by the US FDA. Domestic and foreign clinical studies have shown that the drug is safe and effective in the treatment of depression, with good patient compliance, which is conducive to the long-term maintenance treatment of depressed patients.
(2) Trazodone
Trazodone is a drug that has been clinically used for many years. It has obvious antidepressant and sedative effects, as well as anxiolytic effects, and has little effect on sexual function, and can even treat male erectile dysfunction. Trazodone is easily absorbed orally, with a peak blood concentration time of about 1 hour to 2 hours, an elimination half-life of 5 hours to 9 hours, and a plasma protein binding rate of 89% to 95%. It is suitable for elderly patients and patients with anxiety and insomnia. Commonly used therapeutic dose is 100mg~300mg daily.
(3)Mirtazapine
In the normal dose range, the drug shows linear pharmacokinetics, and the recommended starting dose is 15mg per day, taken once at bedtime. The effective dose is 15mg to 45mg per day. for patients with liver and kidney disease, the clearance of the drug can be reduced by 30% and 30% to 50% respectively, and the clearance of elderly patients is also reduced, so the dosage should be reduced. The drug has almost no effect on sexual function.
The limitations or disadvantages of using antidepressants include the inability of the drug to change the patient’s original low-level or faulty cognitive structure, and its inability to resolve the patient’s latent psychological complexes; its effects are limited and unsustainable. It does not help the patient to achieve the goal of spiritual growth [2].