Psychopharmacology is the study and use of medications that treat psychiatric disorders (American Society of Clinical Psychopharmacology, n.d.). The goal of psychopharmacology is to help regain proper balance in the brain's chemistry and restore optimal functioning (Boland et al., 2021). The use of medications for the mind is, therefore, in most instances, directed towards the control of symptoms. Psychiatric medications are not like antibiotics. Medications alone seldom result in a permanent “cure” of mental or emotional troubles. This means that most psychiatric type medications will need to be taken or be available over an extended period of time while other treatments or therapy seek a resolution to the problem causing the symptoms.
Medications for depression are not as effective as medications for many other conditions.
Follow-up of the effectiveness of antidepressant use is critical because the FDA suggests that all agents with antidepressant properties may increase the risk of suicide – especially in patients under the age of 25.
Many different medication choices are available for the management of depression. Medications used to manage depression work mainly by altering the chemicals in the brain, particularly serotonin, norepinephrine, and dopamine. Medications take a period of time before they work. The effect may be noticed as early as one to two weeks, but it typically requires four to six weeks before a significant effect is noticed.
Antidepressant Medication: Several classes of antidepressant medication exist, grouped together by the neurotransmitter they primarily affect. Antidepressant groupings include:
- Monoamine Oxidase Inhibitors
- Norepinephrine Dopamine Reuptake Inhibitor
- Selective Serotonin Reuptake Inhibitors
- Serotonin Modulators
- Serotonin Norepinephrine Reuptake Inhibitor
- Tricyclic Agents
Monoamine Oxidase Inhibitors: Monoamine oxidase is an enzyme that breaks down neurochemicals such as serotonin, dopamine, and norepinephrine (Boland et al., 2021). Medication that inhibits the degradation of these neurotransmitters promotes higher mood levels by increasing the quantity of available neuroactive chemicals.
MAOIs have been found to be effective in a broad range of anxiety and mood disorders, especially depression. However, due to the risk of hypertensive crisis, practitioners must be very selective in whom they prescribe MAOIs. The client must be able to understand potential risks and follow a very strict, low-tyramine diet.
MAOIs are useful in treating “atypical” depression (e.g., depression with hyperphagia, hypersomnia, leaden paralysis, or rejection sensitivity). Clinicians should also consider the MAOIs for use in clients exhibiting treatment-resistant depression.
Table 7: Monoamine Oxidase Inhibitors (Hirsch & Birnbaum, 2021)
|Name (Generic)||Brand Name ||Elimination Half-life (hours)||Dietary Restrictions|
|Selegiline (transdermal patch)||Emsam®||1.2||No – however, caution advised if exceeding recommended dosages|
MAOIs are effective yet currently not a first-line drug due to a range of severe food-drug and drug-drug interactions that accompany them (Boland et al., 2021).
Table 8: Monoamine Oxidase Inhibitor Interactions (Boland et al., 2021)
|Food Interactions (Tyramine containing foods)||Drug Interactions|
- Aged cheese
- Aged, smoked, or pickled meats
- Yeast extracts
- Wine (red more than white)
- Selective serotonin reuptake inhibitors (SSRIs)
- All serotonergic agents
|Interaction symptoms are similar and represent the effects of excessive catecholamine neurotransmitters in the body: Hypertension, Tachycardia, Tremors, Hyperthermia, and Seizures.|
Norepinephrine Dopamine Reuptake Inhibitors: Bupropion is an antidepressant distinctly different from the others, and specifically listed as an atypical agent for treating depression. Chemically its structure resembles that of amphetamines and has the ability to increase available levels of the “brain reward” neurotransmitter dopamine. A spotty past has led to some hesitancy among prescribers.
Table 9: Norepinephrine Dopamine Reuptake Inhibitors (Rush, 2021)
|Name (Generic)||Brand Name||Starting dose, mg/day|
|Bupropion SR||Wellbutrin SR®||150|
|Bupropion XL||Wellbutrin XL®||150|
Selective Serotonin Reuptake Inhibitors and Serotonin Modulators: Serotonin abnormalities are linked to many emotional and behavioral disorders, including mood disorders, obsessive-compulsive disorder, and aggressive behaviors (Boland et al., 2021).
The selective serotonin reuptake inhibitors (SSRIs) can effectively increase the amount of available serotonin within the brain (Stahl, 2014). Increased levels of serotonin occur quickly after initiation of medication therapy. Initial medication response may be seen in about two weeks; however, the full effect may not be observed for up to eight weeks from initiation of treatment (Stahl, 2014).
Overall efficacy between the SSRIs in relieving depression appears similar. The choice of agent should be determined by matching medication characteristics with individual needs. Serotonin modulators (e.g., nefazodone, trazodone) are similar to SSRIs, though they operate by a slightly different mechanism. Special caution is indicated when liver damage is present due to the manner in which the body metabolizes these agents.
Table 10: Selective Serotonin Reuptake Inhibitors (Rush, 2021)
|Name (Generic)||Brand Name||Starting dose, mg/day||Usual dose, mg/day|
|Fluvoxamine CR||Luvox CR®||100||100-200|
|Paroxetine CR||Paxil CR®||25||25-50|
|Serotonin Modulators (Rush, 2021)|
Table 11: Serotonin Syndrome (Boland et al., 2021)
Serotonergic activity in the central nervous system
- The majority of cases of serotonin syndrome present within 6 to 24 hours of a change or initiation of a drug
- Serotonin syndrome is a clinical diagnosis based on observation as no laboratory test is available to confirm the diagnosis
- Typical vital sign abnormalities include;
- Tachycardia and hypertension
- Severe cases may develop hyperthermia and rapid, dramatic swings in pulse and blood pressure
- Physical examination findings include;
- Hyperthermia, agitation, ocular clonus (rapid repetitive contractions and relaxations in a muscle), tremor, akathisia (uncontrollable limb and body movements), deep tendon hyperreflexia, inducible or spontaneous clonus, muscle rigidity, dilated pupils, dry mucus membranes, increased bowel sounds, flushed skin, and diaphoresis
Treatment of serotonin syndrome includes;
- Discontinuation of all serotonergic agents
- Supportive care aimed at normalization of vital signs
- Sedation, usually with benzodiazepines
- Possible administration of serotonin antagonists (e.g., Cyproheptadine, a histamine-1 receptor antagonist)
Fluoxetine (Prozac®) is dosed at 20 mg in the morning and can be increased up to 80 mg a day. Each titration must occur after a few weeks on the medication. It is not indicated for those less than eight years old. Fluoxetine has a long half-life and is less likely to lead to withdrawal symptoms if abruptly discontinued. A weekly formulation is available that is dosed 90 mg once a week (Stahl, 2014).
Fluoxetine can increase the levels of warfarin, phenytoin, carbamazepine, TCAs, and benzodiazepines. It may lower the therapeutic effect of codeine. It may cause serotonin syndrome when combined with other SSRIs and other antidepressants. It is pregnancy category C. Pregnancy category C means that in animal studies adverse effects on the fetus were found; however, there are no adequate human studies, and the potential benefits of the drug may outweigh the potential risks (Stahl, 2014).
Sertraline (Zoloft®) is started at 25-50 mg orally every day, and the dose can be increased gradually to a maximum of 200 mg per day. It is not indicated for those less than six-years-old. Zoloft® is a common first-line drug for depression and is associated with few side effects. Common side effects include dizziness, fatigue, headache, insomnia, somnolence, diarrhea, nausea, tremor and diaphoresis. It may interact with warfarin, cimetidine, digoxin and diazepam. It is indicated for major depressive disorder, premenstrual dysphoric disorder, panic disorder, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD) and social anxiety disorder (Stahl, 2014).
Paroxetine (Paxil®) has a short half-life and may lead to discontinuation syndrome when the medication is stopped or doses are missed. It has the strongest anticholinergic effects of any of the SSRIs. For major depression, the standard form is dosed 20 mg per day to start to a maximum of 50 mg orally per day, and the extended-release form (Paxil CR®) is dosed at 25 mg once a day to a maximum of 62.5 mg orally every day (Rush, 2021).
Paroxetine is indicated for major depressive disorder, panic disorder, OCD, social anxiety disorder, generalized anxiety disorder, PTSD, and premenstrual dysphoric disorder. Side effects include somnolence, insomnia, dizziness, headache, nausea, xerostomia, constipation, diarrhea, weakness, tremor and diaphoresis. Sexual dysfunction is most problematic with paroxetine among the SSRIs (Williams & Nieuwsma, 2020, Stahl, 2014)
Fluvoxamine (Luvox®) is approved for obsessive-compulsive disorders but is frequently used off label in treating depression and anxiety. The starting dose for adults is usually 50 mg once a day and has multiple drug interactions, including benzodiazepines (Stahl, 2014).
Citalopram (Celexa®) is indicated for depression and is dosed at 20 mg once a day, and the dose can be increased to 40 mg once a day after one week. It interacts with macrolide antibiotics, cimetidine, azole antifungal, omeprazole and carbamazepine. Side effects include: sleep disturbance, xerostomia, nausea and diaphoresis (Stahl, 2014).
Escitalopram (Lexapro®) is dosed at 10 mg once a day and can be increased to 20 mg after one week. It has few interactions but may interact with other SSRIs, cimetidine and alcohol. It is pregnancy category C. The FDA warns that both citalopram (more than 40 mg/day) and escitalopram (more than 30 mg/day) have the potential to prolong the QT interval, and may be fatal. They should be used cautiously in those with underlying heart disease and those who are prone to becoming hypokalemic (Rush, 2021; Stahl, 2014).
Serotonin Norepinephrine Reuptake Inhibitors: Combining the “high alert” system arousal effects of increased norepinephrine with the positive mood benefits of serotonin may be a good combination for some clients struggling with depression. The serotonin-norepinephrine reuptake inhibitors (SNRIs) also tend to have a weak uptake effect. The safety and tolerability of the SNRIs are similar to the SSRIs, although monitoring is warranted for an uncommon sustained rise in blood pressure (Stahl, 2014).
Table 12: Serotonin Norepinephrine Reuptake Inhibitors (Rush, 2021)
|Name (Generic)||Brand Name||Starting dose, mg/day||Usual dose, mg/day|
|Venlafaxine XR||Effexor XR®||37.5-75||75-225|
|Noradrenergic and Specific Serotonergic Antidepressant (Rush, 2021)|
Venlafaxine (Effexor®) comes as an immediate-release form and an extended-release form. The extended-release form is dosed 37.5 to 75 mg a day and can be titrated up to 225 mg a day. The immediate-release form is started at 75 mg divided two to three times a day and titrated up to a maximum of 375 mg a day. It may interact with other antidepressants, cimetidine, diuretics and alcohol. It should not be used in those with severe uncontrolled hypertension. It is pregnancy category C. At doses less than 150 mg a day, it mainly affects serotonin levels, but it affects dopamine and norepinephrine levels at higher doses. Discontinuation syndrome is high with this medication (Stahl, 2014).
Desvenlafaxine (Pristiq®) is a new drug in this class and is dosed 25 to 50 mg once a day for adults. It may be titrated up to 400 mg once a day, but positive effects are not proven with higher doses. Common side effects include nausea, headache, dizziness, dry mouth, insomnia, fatigue and bowel disturbance. It may interact with other SSRIs or blood thinners. It is pregnancy category C (Rush, 2021; Stahl, 2014).
On the first day, Milnacipran (Savella®) is dosed 12.5 mg once a day and is titrated upwards to a maximum of 200 mg a day divided every 12 hours. It should be used cautiously in those with moderate to severe renal impairment and severe hepatic impairment. Those who take it may suffer from nausea, headache, dizziness, sleep disturbance and constipation (Stahl, 2014).
Levomilnacipran (Fetzima®) is started at 20 mg once a day and increased to 40 to 80 mg once a day. The maximum dose is 120 mg a day. Doses needed to be reduced in those with moderate and severe renal insufficiency. Common side effects include nausea but may also be associated with sexual dysfunction, constipation, urinary hesitancy, and elevated heart rate (Rush, 2021; Stahl, 2014).
Duloxetine (Cymbalta®) is dosed 30 mg twice a day to start and may be increased to 30 mg twice a day or 60 mg once a day in adults. The maximum dose is 120 mg a day. It may interact with ciprofloxacin, SSRIs, TCAs, antiarrhythmic agents and anticoagulants. Common adverse effects include nausea, headache, dry mouth, dizziness, sleep disturbance and fatigue (Rush, 2021; Stahl, 2014).
Duloxetine has multiple indications. It is approved for the treatment of depression in addition to diabetic peripheral neuropathy, fibromyalgia and generalized anxiety disorder. This drug is often used by those who have depression in addition to one of these co-morbid conditions (Stahl, 2014).
Mirtazapine (Remeron®) is an antidepressant without a home. It is neither an SSRI nor is it an SNRI. Its effects are similar yet subtly different than either grouping and because of those differences, it should be considered as an option in clients with treatment-resistant depression who are not responsive to SNRI or SSRI medications (Stahl, 2014).
Mirtazapine is dosed 15 mg at bedtime and may be increased every 1-2 weeks up to 45 mg a day in adults. It is given at bedtime because one of its major side effects is sedation. Another common side effect is weight gain. Other side effects include: dry mouth, constipation and dizziness (Rush, 2021; Stahl, 2014).
Tricyclic Antidepressants: Cyclic antidepressants were discovered in the 1950s. The first cyclic antidepressants were named “tri”-cyclic because their chemical structure somewhat resembled three interlocked rings when drawn out in scientific notation. Several other cyclic formulations have been discovered since the days of the three-ringers; however, the tradition carries the name tricyclic forward for the general grouping despite its current descriptive inaccuracy (Hirsch & Birnbaum, 2021)
Cyclic antidepressants find less common use than the current first-line SSRI and SNRI agents. This, in part, is due to a wider neurotransmitter effect, with more brain chemicals being shifted and a resultant broadening of potential side effect profiles (Hirsch & Birnbaum, 2021).
Table 13: Tricyclic Antidepressants (Rush, 2021)
|Name (Generic)||Brand Name||Starting dose, mg/day||Usual dose, mg/day|
Common side effects with TCAs include urinary retention, drowsiness, blurred vision, dry mouth, constipation, orthostatic hypotension, lower seizure threshold and sexual side effects. One major concern with TCAs is that they are more lethal in overdose when compared to newer antidepressants.
The cyclic antidepressants have been associated with occasional cardiac problems. It is highly recommended that before prescribing any of the cyclic agents, a baseline electrocardiogram (ECG) and cardiac history be conducted. In younger clients (less than 40) with a negative cardiac history, the ECG may not be warranted (Hirsch & Birnbaum, 2021)
Treatment is typically started at a low dose and slowly titrated upwards to the therapeutic range. Some response is typically seen within one to two weeks (Hirsch & Birnbaum, 2021). Those individuals that respond early to treatment with antidepressants are more likely to go into remission. Up to three months of treatment is generally recommended to determine if the treatment was effective. In those who have minimal effect after 4-6 weeks, the treatment regime should be reevaluated (Hirsch & Birnbaum, 2021).
Medications need to be continued for at least 6-12 months for them to have lasting effects. If treatment is discontinued early, there is a high risk of relapse. Most antidepressants need to be weaned gradually. Abrupt discontinuation of antidepressants can result in serious side effects known as the discontinuation syndrome. Medications should be discontinued over about two months for those on treatment for 6-12 months and up to 6 months for those on long-term treatment. Gradually tapering the medication is more critical if the patient is on a high dose (Hirsch & Birnbaum, 2021).