Learning Objectives
By the end of this section, you will be able to:
- Describe the biological mechanisms of psychopharmacological drugs
- Differentiate psychopharmacological drug classifications
- Discuss psychopharmacological indications, actions, side effects, interactions, and special populations
- Summarize nursing roles and implications related to psychopharmacological drugs
Nursing is heavily involved in the assessment and management of pharmacological agents. Psychopharmaceuticals are substances that can affect mood, behaviors, feelings, or thoughts. For the most part, assessment of these medications requires careful observation and listening skills applied with a level of understanding of how they work within the human body. This section will provide an overview of the science of pharmacology, the classifications of psychopharmaceuticals, how they work and their adverse effects, information on special populations, and management strategies for nurses.
The Biology of Psychopharmacology
The role of psychopharmacology formally began in the mid-20th century with the invention of chlorpromazine, first used to treat psychotic disorders. The emergence of this drug and further advances in science enabled clinicians to understand the etiology of mental illness better. Health-care providers who contemplate psychotropic medications for their clients consider several variables when choosing a medication: symptom presentation, comorbid disease states, age, gender, genetic variables, which medicines work effectively for which symptoms, potential for side effects and drug-drug interactions, and overall safety. Nursing interventions with psychopharmaceuticals involve education, assessment, management of side effects and adverse events, and being prepared to respond to dangerous drug levels and polypharmacy concerns.
Pharmacokinetic and pharmacodynamic factors determine how a medication will work. What the human body does to a drug is called pharmacokinetics, and what a drug does to the body is called pharmacodynamics. There are four mechanisms included in pharmacokinetics: (1) drug absorption, (2) drug distribution, (3) drug metabolism, and (4) drug excretion.
Drug absorption is the process by which an unmetabolized drug is transported from the site of administration into the circulation system. Distribution is the amount of drug that ends up acting at its target site. This is affected by blood flow, molecular size, and how it interacts with plasma proteins. Drug metabolism is when a drug is broken down or biotransformed by a two-step process. The first step of biotransformation is the first-pass effect when medications undergo extensive hepatic metabolism through enzymatic processes. The result of this process is a reduction in the bioavailability of the medication. Cytochrome P450, also known as CYP450, enzymes often manage this step of the reaction. If a CYP450 enzyme metabolizes a medication, it is called a substrate. Different variables affect the rate of the enzymatic activity of these enzymes. The first is genetic variation. A human can express genetic alterations that inhibit or accelerate the CYP450 enzymes. Additionally, other medications can either induce or stimulate an enzyme. If this occurs, metabolism speeds up. Other drugs can temporarily inhibit or irreversibly inhibit these enzymes. Inhibition causes the metabolism to slow down or, in the case of the irreversible inhibitor, stop altogether. Phase II biotransformation reactions are also known as conjugation reactions that involve the use of transferase enzymes that “detoxify” drugs into excretable forms. Finally, excretion of the drug happens either primarily via the kidneys or the gastrointestinal tract, but can also occur through sweat, saliva, and tears. Factors that can affect excretion include disease states, such as liver disease, kidney disease, and other disease states that can affect blood or urine flow such as congestive heart failure.
The second factor that determines how a medication works is pharmacodynamics, which is the drug-receptor interaction, or how the drug affects the human body in both the nature and strength of its response. Psychotropic drugs usually target neuronal receptors or enzymes, and in doing so, block, imitate, or alter the actions of neurotransmitters. Once a signal from a neuron’s cell reaches the axon terminus, it stimulates the release of a neurotransmitter into the synapse. The neurotransmitter then targets a receptor either at the dendrite of the other nerve or receptor sites on the same nerve. The receptor sites on the same nerve are autoreceptors and shut off neurotransmitters’ flow. Receptors located at the dendritic ends of another neuron serve to either continue the stimulus or shut it down through excitatory or inhibitory neurotransmission.
PMH Drug Classifications
Psychotropics have different classifications: antipsychotics, antidepressants, mood stabilizers, anxiolytics, hypnotics, and stimulants (Table 4.2). Antipsychotic medications mainly block 5-hydroxytryptophan (5HT) dopamine receptors. These medications are approved for use in psychotic disorders and mood stabilization. Antidepressant medications primarily target 5HT or serotonin. These medications treat depression, anxiety, trauma, and obsessive-compulsive disorders. Mood stabilizers have unknown mechanisms of action. These medications are indicated for use in bipolar disorders. Anxiolytics, used for anxiety disorders, include benzodiazepines, which enhance the inhibitory effects of GABA-A receptors; medications like hydroxyzine that block histamine; and Buspirone, which targets serotonin. Medications that work predominantly to increase norepinephrine and dopamine are divided into stimulants and non-stimulants. These medications are used to treat attention-deficit hyperactivity disorder and sleep-wake disorders. Hypnotics work on various sleep-wake receptors and are approved for use in circadian rhythm disorders and insomnia.
| Drug Classification | Subclassification | Name of Drug |
|---|---|---|
| Antipsychotics | 1st generation | Fluphenazine, haloperidol, thorazine, chlorpromazine, thioridazine |
| 2nd generation | Clozapine, risperidone, asenapine, iloperidone, lamotrigine, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, ziprasidone | |
| 3rd generation | Aripiprazole, cariprazine, brexiprazole, lumateperone | |
| Antidepressants | Tricyclics | Imipramine, amitriptyline, nortriptyline, protriptyline, doxepin, desipramine, trimipramine |
| MAOI | Isocarboxazid, phenelzine, selegiline, tranylcypromine | |
| SSRI | Fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram | |
| SNRI | Duloxetine, venlafaxine, desvenlafaxine, levomilnacipran | |
| NDRI | Bupropion | |
| Multimodal | Vortioxetine, vilazodone | |
| Others | Trazodone, mirtazapine | |
| Anxiolytics | Benzodiazepines | Alprazolam, chlordiazepoxide, diazepam, lorazepam, oxazepam, clonazepam |
| Others | Buspirone, hydroxyzine | |
| Hypnotics | GABAergic | Zolpidem, eszopiclone, zaleplon |
| Benzodiazepines | Quazepam, estazolam, triazolam, temazepam | |
| Orexin agents | Suvorexant | |
| Melatonergic | Ramelteon | |
| Stimulants | Nonstimulants | Guanfacine, Atomoxetine |
| Stimulants | Amphetamine (d, l), amphetamine (d), methylphenidate (d, l), methylphenidate (d), lisdexamfetamine, serdexmethylphenidate | |
| Mood stabilizers | Voltage channel blockers | Valproate, carbamazepine, lamotrigine, lithium |
Antipsychotics
To understand the medications that treat psychotic disorders, such as schizophrenia and schizoaffective disorder, it is helpful to have a working knowledge of the etiology of one of the psychotic disease states: schizophrenia. There are three general hypotheses for the causes of schizophrenia. The first posits that dopamine hyperactivity in the brain’s mesolimbic pathway causes the positive symptoms of schizophrenia, which are those that the disease has “added” to the person, such as hallucinations or delusions (see Chapter 15 Schizophrenia Spectrum Disorder and Other Psychotic Disorders). The second hypothesis involves the neurotransmitter glutamate, the major excitatory neurotransmitter in the brain. The theory holds that a hypofunction, formed in the early years of neurodevelopment in the NMDA receptors located on glutamatergic neurons is the cause of schizophrenia. The final theory involves hyperfunction (too much activity) at serotonin receptors. The downstream effect of both hypofunction in glutamate and hyperfunction at serotonin receptors could result in hyperactivity in the same mesolimbic dopamine pathway, which can lead to psychosis.
The development of the first class of antipsychotics was an accident. The phenothiazine class of medications was designed to act as a preanesthetic medication by manipulating antihistamine. The original medication was found to have a calming effect on clients. Research continued until chlorpromazine was invented. It was trialed successfully for the first time with a client with symptoms of mania. With the advent of chlorpromazine, the first generation of antipsychotics arrived. These medications included haloperidol, trifluoperazine, thioridazine, and fluphenazine. Classified as “first-generation antipsychotics or typical antipsychotics” in the 1950s, these medications primarily block dopamine receptors. The first “second-generation antipsychotic” was developed in the mid-1970s. The mechanism of action differed from the first generation in that it had dual actions at both serotonin and dopamine receptors. The second-generation drugs boasted fewer extrapyramidal symptoms (EPS), which are drug-induced movement disorders. Some clients continued to experience them, however, with additional metabolic side effects, such as weight gain, insulin resistance, and hyperlipidemia. Finally, a third generation of atypical antipsychotics emerged. These drugs have more potent actions at serotonin receptors; potentially partial agonism at dopamine receptors or low occupancy at dopamine receptors, which reduces the potential for EPS; and sometimes minimal affinity for histamine receptors, which can result in limited weight gain and metabolic syndrome.
Indications
Antipsychotic medications are indicated (FDA approved) for use in clients who have a diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder (mania, mixed mania, bipolar maintenance, bipolar depression), psychotic disorders, tics, and vocal utterances. They are also indicated for use in Tourette’s syndrome, severe behavior problems in children, and treatment-resistant depression.
Side Effects and Interactions
The undesirable effects of a medical treatment or drug are called side effects. The side effect profiles of typical and atypical antipsychotics are different, but they have two general categories of side effects in common: metabolic side effects and extrapyramidal side effects (Table 4.3). Metabolic side effects include weight gain, insulin resistance, and hyperlipidemia. The exact mechanism of this has yet to be discovered. The second shared side effects category is extrapyramidal side effects (EPS), or drug induced movement disorders. Extrapyramidal side effects include akathisia, dystonia, tardive dyskinesia, pseudo-Parkinson’s, and neuroleptic malignant syndrome. A blockade of dopamine in the mesolimbic nigrostriatal pathway causes these movement disorders. All antipsychotic medications can potentially cause these movement disorders, some more than others. For example, first-generation antipsychotics, such as haloperidol, have more potential to cause EPS than second-generation antipsychotics like lurasidone. The more a medication blocks dopamine, the more potential it has to cause EPS. All antipsychotic medications can be sedating, may cause dizziness, and can lower the seizure threshold. Other significant side effects reported with first-generation antipsychotics include anticholinergic side effects: dry mouth, constipation, blurred vision, and urinary retention. Galactorrhea and amenorrhea are of particular concern for clients. Second-generation antipsychotics have less potential for anticholinergic side effects.
| Extrapyramidal Side Effect | Symptoms |
|---|---|
| Akathisia | Subjective complaints of leg or arm movements, rocking, pacing, feeling restless like they cannot sit still Develops within the first few weeks of starting or increasing dose of medication or reducing or removing a medication that is used to mitigate EPS |
| Dystonia | Involuntary contractions and spasms of the muscles, painful, starts in the face, neck, shoulders Develops within hours to days of starting or increasing dose of medication or reducing or removing a medication that is used to mitigate EPS |
| Tardive dyskinesia | Involuntary facial movements, sucking, chewing, lip smacking, tongue protruding, blinking eyes; also affects the body and extremities Develops within months or years |
| Pseudo-Parkinson’s | Shuffling gait, stiff facial muscles, tremors, bradykinesia, akinesia Develops within a few weeks of starting or increasing a dose of medication or reducing or removing a medication that is used to mitigate EPS |
| Neuroleptic malignant syndrome | High fever (102–104 degrees Fahrenheit), irregular pulse, tachycardia, tachypnea, muscle rigidity, confusion, hypertension, diaphoresis This is a medical emergency |
Most antipsychotic medications have interactions with other dopamine agonists, such as levodopa. They may also cause additional CNS depressant effects when taken with other medications that cause sedation. Additionally, they have the potential to lower blood pressure, which may heighten the effects of antihypertensive agents. Certain antipsychotics contain an enzyme that interacts with cigarette smoking to increase the metabolism of the medication. Therefore, if the client is smoking, or stops smoking, the drug dosages may need to be adjusted.
Clozapine is a second-generation antipsychotic that can potentially suppress bone marrow and cause agranulocytosis, a condition characterized by a low number of white blood cells called granulocytes. It is a severe form of neutropenia. Clients on clozapine are monitored for this risk via a Risk Evaluation and Mitigation Strategy (REMS) program that the Food and Drug Administration requires. Certified providers enroll clients taking clozapine in the program. The clients are then monitored with absolute neutrophil counts (ANC) via weekly blood draws for the first six months, then every two weeks for the next six months. If the client’s ANCs remain within normal ranges, then they shift to monitoring every four weeks. If the client is found to have low ANC counts, additional monitoring or steps come into play in accordance with the clozapine REMS algorithm.
Special Populations
First- and second-generation antipsychotic medications are approved for use in children for disorders, such as aggression, Tourette’s, and tics. Second-generation antipsychotics are preferred as first-line agents over first-generation antipsychotics due to side effect profiles. For older adult clients, lower doses of first- and second-generation medications are indicated as decreased renal clearance, decreased liver functioning, and decreased cardiac output can create opportunities for altered metabolism. Additionally, these medications should be used with caution for clients with dementia because they have been associated with increased mortality rates.
Nursing Implications
When working with clients who will be starting on antipsychotics, nurses begin with an assessment. They should assess for medications or conditions contraindicated with the medication. Mental status exam and appropriate screening tools are indicated. Nurses should assess for BMI, fasting lipids, fasting glucose, and potential ECG. For clients taking clozapine, there is a risk for severe neutropenia as defined as absolute neutrophil count less than 500/µl. For those clients being initiated and maintained on the medication, nurses should measure baseline blood ANC before starting treatment and during treatment at prescribed times. Several different scales can be used to assess EPS, for instance, like the Extrapyramidal System Rating Scale (ESRS) or the Abnormal Involuntary Movement Scale (AIMS) (Table 4.4). The Simpson-Angus Scale verifies medication-induced Parkinsonism. The Barnes Akathisia Rating Scale identifies antipsychotic-induced akathisia. Once the health-care team identifies, documents, and communicates side effects, they can prescribe medications to mitigate them.
Once an antipsychotic has been prescribed, the nurse should educate the client on the following: drug-drug interactions, medications to avoid, side effects, diet, exercise, monitoring of adverse events, and safety planning strategies. Medications commonly avoided with antipsychotics include other dopamine agonists, such as levodopa. Side effects common with antipsychotics include extrapyramidal symptoms (EPS), metabolic syndrome such as insulin resistance, hyperlipidemia, weight gain, sedation, sexual dysfunction, gastrointestinal upset, orthostatic hypotension, and lowering of seizure threshold. Educating clients on diet and exercise helps to mitigate the risks for weight gain and metabolic syndrome. Nurses should monitor for adherence, efficacy, side effects, adverse events, and client understanding of education.
| EPS | Treatment |
|---|---|
| Dystonia | Benztropine Diphenhydramine |
| Akathisia | Reduction of dose or removal of offending medication Benzodiazepines Propranolol Mirtazapine |
| Pseudo-Parkinson’s | Benztropine |
| Tardive dyskinesia | Reduction of dose or removal of offending medication Valbenazine Deutetrabenazine |
Clinical Safety and Procedures (QSEN)
QSEN Competency: Client-Centered Care
Side effects of antipsychotic medications can occur at any stage of treatment and include the extrapyramidal symptoms (EPS), dystonia, tardive dyskinesia, akathisia, and anti-parkinsonian. Providing client-centered care involves assessing and identifying these adverse events; some symptoms can be irreversible if left unmanaged. Additionally, side effects, such as EPS, are a common reason for non-adherence to antipsychotic agents.
Assessment for symptoms of dystonia on examination and observation include muscle stiffness in upper limbs, head, and tongue and eye rolling. For dyskinesias, check for slow or lateral movements of the tongue and jaw, chewing, biting, clenching, puckering, pouting, and lip smacking, involuntary rocking or twisting of the torso or pelvic gyrations, uncontrollable slow “pill rolling” of hands, shuffling gate, and slow-moving lower limbs. For akathisia, look for uncontrollable urges to move legs relieved by standing and walking, inability to sit still, constant movement or walking. Assess also for subjective level of feelings of uneasiness. Assess client perception of the side effects, if they are noted by the client, how much, and how distressing these symptoms are to the client. Do they interfere with the client’s functioning? Do they influence the client’s willingness to continue the medication?
Tools to evaluate extrapyramidal symptoms include the following: the Extrapyramidal Symptom Rating Scale (ESRS), which assesses for akathisia, dystonia, dyskinesia, and Parkinsonism; the Abnormal Inventory Movement Scale (AIMS), which assesses for tardive dyskinesia; and the Barnes Akathisia Rating Scale, which assesses for akathisia while the client is in a seated position. All signs of EPS should be documented in the client record and promptly transmitted to the provider for medical intervention.
After medical intervention is provided, documentation may include answers to questions such as the following:
- What response does the client have?
- If a medication dose is lowered, does the client show signs of symptoms that have returned as a result?
- If a medication is given to treat the side effects, what response to the medication does the client have?
- Does the client have adherence to their medications?
Accurate assessment of side effects and response to interventions is essential in affording the client confidence with their medications, which translates to adherence to treatment algorithms and positive outcomes.
Link to Learning
Read this research article reviewing assessment scales and describing the necessity of prevention and detection of medication side effects to learn more. Nursing implications include accurate assessments, client education, and nursing awareness of potential side effects with newer drugs marketed as “lower incidence” for side effects.
Antidepressants
Research has not fully explained the etiology of mood disorders. Based on the effects of psychopharmacology (working backwards), one common theory is that deficits in the monoamines contribute to symptoms of depression. As discussed earlier, the monoamines include norepinephrine, dopamine, and serotonin. Antidepressants target monoamines to increase dendritic growth and mitigate mood states. Another theory on the causes of depression is related to stress, genetics, and inflammation. These factors can potentially cause loss of neurons.
The origin of antidepressants is tied to that of antipsychotic agents. The antipsychotic agent chlorpromazine was slightly modified in the 1950s, resulting in the first tricyclic antidepressant, imipramine. Tricyclic antidepressants (TCAs) include imipramine, amitriptyline, nortriptyline, protriptyline, doxepin, desipramine, and trimipramine. These antidepressants increase serotonin and norepinephrine by blocking both presynaptic reuptake pumps. Additionally, these medications block alpha 1 and 2, muscarinic, and histamine receptors.
In March 1982, fluoxetine, the first SSRI was approved by the Food and Drug Administration. Fluoxetine, sertraline, fluvoxamine, paroxetine, citalopram, and escitalopram followed. These medications were novel in both their chemical structure and their safety profile. Tricyclic antidepressants have high lethality in an overdose due to hypotension, cardiac dysrhythmia, seizure, and coma. SSRIs are rarely lethal. These medications block the presynaptic serotonin reuptake pump, resulting in increased serotonin within the synaptic cleft. Other antidepressants followed, with the invention of the serotonin norepinephrine reuptake inhibitor (SNRI), such as venlafaxine and duloxetine; the norepinephrine dopamine reuptake inhibitor (NDRI), such as bupropion; the serotonin receptor antagonist/serotonin antagonist/reuptake inhibitors (S-MM/SARI), such as trazodone; and the serotonin multimodal (S-MM) agents, such as vortioxetine.
The final class of antidepressant drugs, monoamine oxidase inhibitors (MAOI), targets the enzymatic destruction of the monoamines in the synaptic cleft. These medications irreversibly inhibit the enzymes MAO-A and MAO-B from breaking down all three monoamines, resulting in increased neurotransmitter levels in the synaptic space. An example of an MAO-I is phenelzine.
Indications
Antidepressant medications are FDA-approved for depression, most anxiety and obsessive-compulsive disorders, PTSD, panic disorder, social anxiety disorder, premenstrual dysphoric disorder, pain disorders (SNRIs and TCAs, such as duloxetine or amitriptyline), insomnia (doxepin), and Parkinson’s disease (selegiline).
Side Effects and Interactions
Different types of antidepressants cause different types of side effects. Tricyclic antidepressants can potentially cause significant side effects. Because overdose carries a high risk of lethality, use these medications with caution for clients who are suicidal or who are known to have self-harming behaviors. Common side effects of tricyclics include dizziness, sedation, fatigue, anticholinergic side effects (blurred vision, constipation, urinary retention, dry mouth, weight gain), sexual dysfunction (impotence in biological men, decreased libido in biological women), headache, irritability, and nervousness. Dangerous side effects include paralytic ileus, hyperthermia, the potential for seizures, hypotension, dangerous arrhythmias, increased ocular pressure, activation of mania, and suicidal ideation. These medications are contraindicated in those who have cardiac disease, have undergone cardiac surgery, have arrhythmias, or have had myocardial infarctions. These medications are not recommended with other medications that prolong QT intervals.
Clients generally tolerate SSRIs well, and they are rarely lethal in an overdose. Notable side effects include gastrointestinal upset, headache, tremors, insomnia, agitation, dizziness, sweating, decreased platelet aggregation, and sexual dysfunction. Serious side effects include mania; suicidal thoughts and behaviors, especially in those younger than 24 years of age; and decreased seizure threshold. Drug contraindications with SSRIs include MAO inhibitors, and SSRIs should be used cautiously with other serotonergic medications because of the possibility of serotonin syndrome. A potentially life-threatening drug-drug interaction called serotonin syndrome is caused when high levels of serotonin are built up in the body. Signs and symptoms of serotonin syndrome include agitation, restlessness, insomnia, confusion, muscle rigidity, tachycardia, hypertension, dilated pupils, sweating, diarrhea, shivering, and headache. It most often happens after introducing a new serotonergic drug, or increasing the dose of one a client is already taking. Mild cases resolve by decreasing or stopping the offending agent, but more serious cases require emergency measures. Moreover, abrupt discontinuation from SSRIs can cause discontinuation syndrome. A time-limited syndrome caused by sudden cessation or tapering too quickly off of an antidepressant is called discontinuation syndrome. The symptoms can be characterized as mild to moderate and can last from a few days to a few weeks after stopping the medication. Symptoms can include dizziness, imbalance, insomnia, sensory disturbances, flu-like symptoms, nausea, burning, tingling, electric shock-like feelings, irritability, and agitation.
SNRIs, like SSRIs, are generally well tolerated. Due to their blockade at presynaptic norepinephrine transports, however, there is a potential for these medications to affect blood pressure. Serious side effects include mania; suicidal thoughts and behaviors, especially in those younger than 24; and decreased seizure threshold. Drug contraindications with SNRIs include MAO inhibitors; they should be used with caution with other serotonergic medications because of the possibility of serotonin syndrome. Abrupt discontinuation from SNRIs can cause discontinuation syndrome.
Mirtazapine is an atypical antidepressant, frequently taken at night. The medication is more sedating at a lower dose and serves as an antidepressant at higher doses. It is rarely lethal in an overdose. The medication can cause dry mouth, constipation, dizziness, low blood pressure, and significant weight gain. This medication is not for use in a client with a high BMI, and can increase risk for people with narrow-angle glaucoma. Serious side effects include mania; suicidal thoughts and behaviors, especially in those younger than 24; and decreased seizure threshold. The FDA has issued a warning on most antidepressants that there is a potential increased risk of suicide in those clients taking them under the age of 24. Evaluation of suicide risk in all mental health clients is critical to any assessment and involves collaborative care management approaches between family, other health-care providers, educators, and friends. Drug contraindications with mirtazapine include SSRI, SNRI, and MAO inhibitors. It should be used with caution with serotonergic medications because of the possibility of serotonin syndrome. Abrupt discontinuation from mirtazapine can cause discontinuation syndrome.
Bupropion is a norepinephrine and dopamine reuptake inhibitor. It is taken early in the day to avoid late afternoon activation and insomnia. It is rarely lethal in an overdose, but this medication can be abused by crushing and snorting it. Side effects include insomnia, dizziness, agitation, weight loss, high blood pressure, constipation, dry mouth, and nausea. Dangerous side effects include Stevens-Johnson syndrome, tinnitus, lowered seizure threshold, and activation of mania and suicidal behaviors, especially in those younger than 24. This medication is contraindicated in those with preexisting eating disorders, seizure disorder, traumatic brain injury, alcohol or sedative use disorder, or nervous system tumor. This medication is used with caution in those with severe anxiety, bipolar disorder, or severe insomnia because it can be activating. For instance, it can cause activation or mania in a client who is diagnosed and being treated for a unipolar depression but who has an underlying bipolar process. Monitor for signs and symptoms of hypomania or mania, which can include decreased need for sleep, pressured speech, impulsive behaviors, distractibility, tangential behaviors, racing thoughts, and grandiosity.
Trazodone is a serotonin receptor antagonist and, like mirtazapine, is taken at night. The medication may be used for sleep at a lower dose and serves as an antidepressant at higher doses. It is rarely lethal in an overdose. Side effects include GI issues (nausea, vomiting, constipation, dry mouth), blurred vision, dizziness, fatigue, headache, low blood pressure, tremors, and rare rash. Serious side effects include priapism; mania; suicidal thoughts and behaviors, especially in those younger than 24; and decreased seizure threshold. Drug contraindications include MAO inhibitors, and this drug should be used cautiously with other serotonergic medications because of the possibility of serotonin syndrome. Use is cautioned in people with narrow-angle glaucoma, due to mydriatic activity of the drug, which can increase intraocular pressure. Abrupt discontinuation from trazodone can cause discontinuation syndrome.
Multimodal antidepressants have more than a single effect, that is, inhibiting and activating at receptor sites. This class of medications has properties at various locations on serotonin receptors. They have the lowest potential for side effects. Reports of lethality in overdose are rare. Side effects include GI issues (nausea, diarrhea, vomiting, dry mouth), insomnia, dizziness, sexual dysfunction, and antiplatelet aggregation. Serious side effects include mania; possible activation of suicidal thoughts and behaviors, especially in those younger than 24; and decreased seizure threshold. Drug contraindications include MAO inhibitors, and these drugs should be used cautiously with other serotonergic medications because of the possibility of serotonin syndrome. Abrupt discontinuation from SSRIs can cause discontinuation syndrome. Collaborative practice decisions should be made concerning SSRI use prior to surgery. Risk for perioperative bleeding as well as risks of discontinuation syndrome and depression relapse must be balanced with benefit of continued symptom management in mood disorders.
MAO inhibitors, the final class of antidepressants, irreversibly block the enzymatic activity of MAO-A and B. There can be life-threatening side effects if a client on MAO inhibitors ingests food containing tyramine (Table 4.5)—which can cause a hypertensive crisis—or medications that require the enzymatic destruction of MAO A/B. Signs and symptoms of the hypertensive crisis include rapid or precipitous increase in blood pressure, sweating, anxiety, headache, and nausea and vomiting.
| Category | Examples |
|---|---|
| Food high in tyramine | Strong or aged cheeses Cured meats Smoked or processed meats Pickled or fermented food, like sauerkraut and kimchee Soybeans, fava beans, snow peas, tofu Tap beer Yeast spread, brewer’s yeast Meat tenderizers, soy sauce, teriyaki sauce, miso, shrimp, and fish sauce Dried or overripe fruits |
| Drugs | All other antidepressants Meperidine Sympathomimetic agent Guanethidine Other serotonergic agents: tramadol, Zofran, carbamazepine, methadone, migraine medications, such as sumatriptan Some antipsychotics, such as ziprasidone St. John’s Wort Dextromethorphan and other decongestants Drugs of abuse: MDMA, cocaine, methamphetamine Certain types of alcohol (talk to the health-care provider_ |
Special Populations
SSRIs and SNRIs have been proven safe and effective in most clients above age six, but it is important to weigh the risks versus the benefits carefully when considering SNRIs and TCAs for this population. MAOIs are not for use in clients under the age of 16. Multimodal agents, such as vortioxetine, have not been established as safe or effective in children. SSRIs and SNRIs can be safe and effective in older adult populations. Those recovering from cardiac surgery and those diagnosed with arrhythmias or CVAs should generally be prescribed an SSRI, which will not exacerbate the condition.
Nursing Implications
Nurses caring for clients who take antidepressants should assess for medications or conditions that are contraindicated with the antidepressant. For clients taking bupropion, for instance, the assessment should include a history of any preexisting seizure disorders, head injury, or eating disorders contraindicated for the medication. Nurses should assess client suicidality through evidenced-based suicide assessment tools, such as the Columbia Suicide Severity Rating Scale. Nurses should use a collaborative approach with the client to develop a suicide safety plan and educate on the national suicide hotline at 988. They should limit access to certain antidepressants to clients who are at risk of self-harming behaviors. Nurses should educate clients on potential for drug/drug interactions, such as over-the-counter medications or herbal remedies like St. John’s wort. For those clients taking MAOIs, education includes dietary restrictions and medications to avoid, such as over-the-counter cold medications to avoid antihypertensive crisis. Nurses should document any side effects or adverse events related to the medication and notification to the provider. They should also assess changes in condition once medical intervention has taken place and document the response. Nurses should use motivational approaches to manage nonadherence to medication.
Clinical Judgment Measurement Model
Psychopharmacology
The Clinical Judgment Measurement Model is an evidence-based model that identifies six cognitive skills needed to make appropriate clinical judgments. Consider these skills in the context of psychopharmacology.
A nurse works in a clinic with clients diagnosed with severe mental illness. Client X, a 57-year-old, presents to the clinic two days after converting from risperidone PO to risperdal consta injection. The client is complaining of muscle stiffness, sore jaw, sore neck, and an inability to close their mouth. The client’s eyes are rolling back into their head. They are having difficulty talking.
1. Recognize cues: Gather information, such as medication history, signs, symptoms, health history, and so forth.
2. Analyze cues: How does the client history and signs/symptoms relate to the client presentation and the client’s needs or concerns?
3. Prioritize hypotheses: Establish priorities based on the client’s needs or problems. The priority here is the side effects from the antipsychotic medication. The client recently had a change to the dosing of their medication that may have contributed to the current symptoms.
4. Generate solutions: Identify outcomes and nursing interventions to meet the client’s needs or address the problems.
Expected outcome: Reduction in the adverse events related to possible medication reaction.
Nursing interventions: Assess for EPS using scale, take vital signs, notify provider, monitor client per agency policy, administer medications as indicated, evaluate the effects of the medications by reassessing the client one hour postadministration.
5. Take action: Implement the nursing interventions using priorities of care and planned outcomes to promote, maintain, or restore the client’s health. Collaborate with other members of the health-care team, and participate in coordination of care by implementing the plan of care, documenting care, giving/receiving report, assisting with rounding, educating the client, and so forth.
6. Evaluate outcomes: Gauge the client’s response to the interventions to see if the outcomes have been met. If met, continue to monitor. If not met, gather more information and/or revise the plan of care.
One hour post medication administration, the client is now able to move their mouth without soreness, is able to talk, and has no muscle stiffness or soreness after injection.
Mood Stabilizers
Mood stabilizers are used to treat bipolar mood disorders and differ from medications to treat unipolar depression. Mood stabilizers help mitigate both the highs of mania and the lows of depression. The biological etiology of bipolar disorder, like unipolar depression, is unknown. A possible genetic determinant has been linked to CACNA1C2, a gene that affects the amygdala, responsible for emotions. As with depression, deficits in neurotropic factors, stress, and inflammation have also been linked to the disease. There are three types of medications used to treat bipolar disorder: antipsychotic medications, as already discussed, lithium, and anticonvulsants.
Lithium
The mechanism of action for lithium is unknown. It is considered to be a first-line choice in the management of mania and mixed mania, and with bipolar maintenance. There is also evidence linking lithium to a reduction in suicidal thoughts. Lithium is a salt and is excreted via the renal system. Therefore, clients should have optimal renal functioning to take this medication. Lithium also requires monitoring trough blood levels 12 hours after the last dose. Optimal lithium levels fall between 0.6 to 1.2 mEq/L. Side effects include ataxia, mild tremors, thirst, frequent urination, weight gain, acne, hair loss, and euthyroid goiter. Lithium toxicity can start when blood levels reach 1.5 mEq/L, with severe toxicity (which is life-threatening) at 2.5 mEq/L and above. Dangerous and life-threatening side effects include lithium toxicity, seizures, diabetes insipidus, arrhythmias, and renal impairments. This medication is contraindicated for those with renal impairments, those who suffer from cardiac disease, and clients with sodium depletion or who are severely dehydrated (Table 4.6). Medications to avoid taking in conjunction with lithium include NSAIDs; COX-2 inhibitors, such as celecoxib, metronidazole, calcium channel blockers, ACE inhibitors, and diuretics.
| Signs and Symptoms | Lithium Levels | |
|---|---|---|
| Mild to Moderate | Nausea, vomiting, diarrhea, tremors, fatigue, drowsiness, weakness | 1.5–2.5mEq/L |
| Severe | Agitation, hyperthermia, tachycardia, hypotension, confusion, delirium, slurred speech, renal failure, coma, death | 2.5–3.5 mEq/L and above |
Anticonvulsants
Anticonvulsants are another type of mood stabilizer that includes valproic acid, lamotrigine, and carbamazepine. While the exact mechanism is not known, these medications target voltage-sensitive sodium channels. The end goal is the overall reduction in excitatory neurotransmission at the synaptic cleft, which results in mood stabilization. Valproic acid is the only anticonvulsant mood stabilizer that requires monitoring of trough blood levels. The therapeutic range for valproic acid is 50–125 µg/mL, with toxic levels > 150 µg/ML. Side effects of valproic acid include sedation, GI issues (nausea, vomiting, diarrhea), weight gain, and alopecia. Adverse events associated with valproic acid include activation of suicidal thoughts, hepatotoxicity, tachycardia, and valproic acid toxicity. Signs and symptoms of valproic acid toxicity include nausea, vomiting, myoclonus, somnolence, dizziness, hallucinations, irritability, headache, lethargy, respiratory depression, and coma. Drug interactions with valproic acid include lamotrigine, carbamazepine, topiramate, cimetidine, erythromycin, ibuprofen, phenobarbital, and phenytoin.
Link to Learning
Management of lithium levels involves understanding peak and trough levels. Review the details of monitoring lithium from Psych Scene.
Lamotrigine and carbamazepine side effects are sedation, dizziness, nausea, constipation, and blurred vision. Adverse reactions for both include activation of suicidal ideation and potential for Stevens-Johnson syndrome. Carbamazepine has the potential to cause aplastic anemia and agranulocytosis. Drug interactions with lamotrigine include valproic acid, oral contraceptives, phenobarbital, phenytoin, and lithium. Drug interactions with carbamazepine include hormonal contraceptives, other anticonvulsants, and lithium.
Special Populations
Lithium is not indicated for mood stabilization for children under seven, and valproic acid is not for children under the age of 10; lamotrigine and carbamazepine are not indicated for use as mood stabilizers for children at all. All mood stabilizers are indicated for older adult clients with adequate renal and metabolic states. Lithium has the potential to become neurotoxic in older adult individuals, so it should be monitored closely. When initiating anticonvulsants in older adults, low start with low doses, titrate slowly, and monitor closely for safety and efficacy. Use of mood stabilizers during pregnancy and breastfeeding requires medical management.
Nursing Implications
Nurses caring for clients taking mood stabilizers should assess for medications or conditions that might be contraindicated with the mood stabilizers. They should also assess client suicidality through evidenced-based suicide assessment tools, such as the Columbia Suicide Severity Rating Scale, and should limit access to mood stabilizers to those who are at risk of self-harming behaviors. Nurses should educate clients on the following: drug-drug interactions, medications to avoid, side effects, monitoring of adverse events, and safety planning strategies. Monitor adherence, efficacy, side effects, adverse events, and client understanding of education. Nurses should also monitor baseline BMI, labs, and blood pressure, and should continue with trough blood levels for valproic acid and lithium. Nurses should report signs and symptoms of lithium and valproic acid toxicity. Nurses should educate clients on lithium on the importance of maintaining adequate hydration, not overhydrating, and on the signs and symptoms of toxicity.
Anxiolytics
Anxiolytics, or antianxiety drugs, are a class of medications that decrease anxiety. This class includes benzodiazepines, buspirone, and hydroxyzine. Benzodiazepines are positive allosteric modulators on the GABA receptor. They increase the flow of negative ions through the cell wall of the neuron to allow for more inhibitory actions. In effect, this will directly oppose the excitatory nature of the brain. It “slows things down” and decreases the sensory flow of information to the brain. These medications have a variety of duration of actions and a potential for dependence and abuse. Buspirone is a serotonin receptor partial agonist, but the mechanism of action is unknown. The medication is given two to three times a day, requires several weeks to work, and is usually prescribed as an adjunct to another medication. Hydroxyzine is a histamine antagonist and is classified as an antihistamine. The medication is given two to three times a day as needed for anxiety.
Indications
Most benzodiazepines are indicated for short-term treatment for generalized anxiety disorders, anxiety, and panic. Some are indicated only for insomnia. Buspirone is indicated for long-term anxiety management, whereas hydroxyzine is used as an as-needed medication for anxiety.
Side Effects and Interactions
Side effects of benzodiazepines include sedation, dizziness, fatigue, and confusion. There is the potential for these medications to cause a paradoxical reaction, a heightened anxiety, excitability, and nervousness. All benzodiazepines have the potential to create tolerance and cause abuse. Abrupt discontinuation of long-term use of benzodiazepines can result in withdrawal seizures. These medications are tapered slowly to alleviate that dangerous situation. Adverse reactions include CNS depression and overdose. Clients with closed-angle glaucoma should not take benzodiazepines. These medications also should not be given to clients who have alcohol use disorder unless the client is under medical supervision for alcohol withdrawal treatment.
Side effects of buspirone include sedation, headache, nervousness, excitement, drowsiness, and insomnia. Dyskinesias are possible with this medication. Adverse reactions are rare but can include cardiac symptoms. Drug interactions include any serotonergic medication that can cause serotonin syndrome. Hydroxyzine side effects include sedation, fatigue, dizziness, and QT prolongation. Drug interactions with this medication include any medication that causes QT prolongation, such as escitalopram, citalopram, or ziprasidone. This medication should be used with caution in clients with any known cardiac disease.
Special Populations
Benzodiazepines are not frontline medications for children and may have paradoxical effects. There is limited information on the efficacy of buspirone for children over the age of six, so it is usually not prescribed in pediatrics. Hydroxyzine can be used for children over six in divided doses while monitoring for paradoxical effects. Benzodiazepines and buspirone can be used for anxiety in older adults, with lowered doses and monitoring for clearance, cognitive impairment, and fall risk. Hydroxyzine should not be prescribed to older adult clients with cardiac disease or those with dementia. Lower doses should be given to all other older adult clients while monitoring for clearance, cognitive impairment, and fall risk.
Life-Stage Context
Medications for Older Adults
The American Geriatric Society publishes a guideline called the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults, most often referred to as the Beers List. This evidenced-based approach provides information to health-care providers on the safe management of medications of adults ages 65 and older. The list is divided into categories of medications that might cause adverse effects or have limited effectiveness, and those medications that are contraindicated with certain disease states.
Assessment of medications for those 65 and older begins with medication reconciliation: obtaining a list of client medications, asking the client about current medications—including over-the-counter and supplements—and changes to prescribed medications. Assessment continues with identifying medications listed in the Beers List and the potential complications: drug-drug interactions, potential for adverse events, or contraindications with current disease states. The next step is to educate clients on the potential for adverse events. For example, if the client has impaired mobility and the medication causes CNS depressant effects like dizziness, the situation warrants educating the client on managing falls. Ensure health literacy of client education through return communication of the education received. Assessment and management of medications for those over the age of 65 is part of client safety and best practices for which nurses are responsible.
Nursing Implications
Nursing management of clients taking anxiolytics starts with an assessment for medications or conditions that might be contraindicated with the medication. It continues with the nurse educating the client on the following: drug-drug interactions, medications to avoid, side effects, monitoring of adverse events, and potential for tolerance and dependence for those who are taking benzodiazepines. Nurses should monitor adherence, efficacy, side effects, adverse events, and client understanding of education. Clients taking benzodiazepines should be taught not to abruptly stop the medication if they have been using it long-term. When they do discontinue, nurses should monitor for signs and symptoms of withdrawal, which can occur within 24 to 48 hours after the last dose depending on the half-life of the benzodiazepine, using a scale like the Clinical Institute Withdrawal Assessment Scale. Alternative benzodiazepines may be ordered to ameliorate the alcohol withdrawal symptoms. Signs and symptoms of benzodiazepine withdrawal include anxiety, nausea, tremors, diaphoresis, headache, heart palpitations, hallucinations, depression, autonomic instability, and seizures.
Hypnotics
Hypnotics are a class of medications that help clients fall and stay asleep. Sleep is a biological process that involves a homeostatic and circadian drive. Neurotransmitters involved in these processes include those that stimulate sleep like melatonin and GABA and those involved in the wake cycles, such as acetylcholine, dopamine, serotonin, norepinephrine, and histamine. There is an additional neurotransmitter, orexin, that promotes the balance between wake and sleep states. Hypnotics have several different targets in the sleep-wake cycle. One medication, ramelteon, works at the melatonin receptor to induce the sleep cycle. The GABA A positive allosteric modulating drugs, such as zolpidem, zaleplon, and eszopiclone, work at the same receptors as the benzodiazepines (but at a different subunit, so they lower the potential for tolerance and dependence) to decrease “excitatory” sensory noise that reaches the brain, allowing the client to sleep. Orexin-targeting medications, such as suvorexant, inhibit wake-promoting neurotransmitters, such as histamine, norepinephrine, and dopamine. These actions allow for stabilization and maintenance of sleep.
Indications
Hypnotics are indicated for sleep onset insomnia, sleep maintenance insomnia, short-term insomnia, and treatment of insomnia with early morning awakening as a symptom.
Side Effects and Interactions
Side effects of hypnotics generally include sedation, dizziness, fatigue, and headache. Medications that work on GABA receptors have side effects, including amnesia and amnestic events, such as sleep eating, sleep driving, sleep cooking, and sleep texting/making phone calls. Adverse events for GABA receptor medications include tolerance and dependence, the potential for CNS depression, and overdose. Adverse events related to orexin agents include the remote potential for tolerance and abuse, sleep paralysis, hallucinations, and cataplexy. Therefore, these medications are generally not for use in those with narcolepsy.
Special Populations
Hypnotic medications have not been proven safe or effective in children. Ramelteon, the melatonergic hypnotic, is safe for use in older adult clients; dose adjustments are not necessary. GABA receptor medications can be used cautiously in older adult clients, but there is an increased risk of falls. Lower doses are generally recommended, and clients should be placed on falls precautions.
Nursing Implications
Nursing management of clients taking hypnotics starts with an assessment for medications or conditions with which the hypnotics might have a contraindication. Educate clients on the following: drug-drug interactions, medications to avoid, side effects, monitoring of adverse events, and potential for tolerance and dependence for those who are taking GABA receptor hypnotics. Monitor for adherence, efficacy, side effects, adverse events, and client understanding of education. Clients taking GABA receptor hypnotics should be educated not to abruptly stop the medication if they have been using it long-term, because it can cause withdrawal anxiety and worsen insomnia. Nurses should monitor for total sleep time, time to fall asleep, number of awakenings during the night, and time to fall asleep after awakenings. Nurses should educate the client on sleep hygiene and nutritional and exercise factors that affect healthy sleep states.
Stimulants
Attention-deficit/hyperactivity disorder (ADHD) is a state caused by the inefficiencies of two significant neurotransmitters, norepinephrine and dopamine, that promote information processing in the brain’s prefrontal cortex. Too much of these neurotransmitters causes overexcitability, inability to concentrate, and a flight or fight response. Conversely, too few neurotransmitters make the client drowsy, inattentive, and sleepy. When these two neurotransmitters work efficiently, the client is alert, awake, and cognitively able to attend to events in their environment. The medications used to regulate these two neurotransmitters for those who have ADHD are called non-stimulants, and they generally work to make the two neurotransmitters work more optimally; the non-stimulants are called guanfacine and atomoxetine. These medications work slower and are not controlled substances. Stimulant medications, by contrast, work within the central nervous system to increase the availability of neurotransmitters by blocking the reuptake transporter into the presynaptic neuron. Stimulants are controlled substances and have the potential for tolerance and dependence. Stimulants are usually considered first-line agents for treating ADHD in school-age children. If caregivers object to stimulant medication and/or there are medical contraindications, however, non-stimulant medications are an option.
Link to Learning
This Berkeley Well-Being video discusses the details of fight or flight as a normative response to a threat in the environment and its links to some mental health symptoms.
Indications
Non-stimulants and stimulants are indicated for treating ADHD, narcolepsy, and excessive sleepiness.
Side Effects and Interactions
Guanfacine is a norepinephrine receptor agonist and a non-stimulant. Side effects of this medication include lowered blood pressure, low pulse, dry mouth, constipation, sedation, fatigue, and nausea. Dangerous side effects include bradycardia. Atomoxetine is a selective serotonin /norepinephrine reuptake inhibitor. Side effects include anorexia, weight loss, tachycardia, hypertension, insomnia, activation, dry mouth, constipation, nausea, urinary hesitancy, sexual dysfunction, and anxiety.
Stimulants take a variety of actions to boost norepinephrine and dopamine within the central nervous system. Side effects include insomnia, weight loss, headaches, tics, dry mouth, Raynaud’s, anxiety, and activation. Adverse events include tachycardia, hypertension, priapism with some stimulants, tardive dyskinesia, neuroleptic malignant syndrome, activation of mania or suicidal thoughts, seizures, and cardiac events. These medications are generally contraindicated in those with severe anxiety, a history of cardiac disease, seizure disorders, tics, glaucoma, and current alcohol or benzodiazepine use disorder. Drug-drug interactions include MAO inhibitors, medications that increase blood pressure, and antihypertensive medications. Use stimulants with caution with mood stabilizers because stimulants may destabilize those with bipolar disorder.
Special Populations
Non-stimulant and stimulant medications are generally not recommended for use in children under the age of six. These medications are not recommended for older adult clients with a cardiac disease history.
Nursing Implications
Nursing management of clients taking non-stimulants and stimulants starts with assessing medications or conditions contraindicated with the medication. Nurses should educate clients on the following: drug-drug interactions, medications to avoid, side effects, monitoring of adverse events, and potential for tolerance and dependence. Nurses should monitor for pulse, blood pressure, height, weight, adherence, efficacy, side effects, adverse events, and client understanding of education. Nurses should educate clients on maintaining nutritional status, especially during midday hours; taking medications when directed; not taking medications too late in the day, which could interfere with sleep; and behavioral strategies to manage attention deficits, such as exercise and structure in the environment.
Link to Learning
Use this comprehensive video on the indications and side effects of psychopharmacological medications as a visual reminder.