Psychopharmacology: Medications for the Mind Course | CEUfast Nursing Continuing Education
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Psychopharmacology: Medications for the Mind

3.00 Contact Hours
A score of 80% correct answers on a test is required to successfully complete any course and attain a certificate of completion.
Author:    David Tilton (RN, BSN)

Purpose/Goals

Medications for the mind have a powerful effect. Important treatments center on altering the chemical balance of the brain. Often, in our fast-paced professional lives, it is difficult to remember the classifications and use of medications seen on an infrequent basis. It is important to routinely refresh our own memory, exercise cognitive processes, and review briefly the medications for the mind, psychopharmacology.

Objectives

On completion of this educational activity, participants will be able to;

  1. Identify two major categories of psychopharmacology agents
  2. Describe the effect desired from Mood Stabilizers
  3. Distinguish how the mechanisms of action vary between antidepressant groups
  4. Explain two uses of psychostimulant medications
  5. Detect correct neurotransmitter functions

Introduction

Psychopharmacology is the study and use of medications that affect thought or behavior. People currently ingest vast quantities of prescription psychopharmaceuticals. The benefit sought from prescription psychoactive agents is the lessening in symptoms of mental or mood disorders, whether acute or chronic in nature. As a general medication category, psychopharmacology agents, especially antidepressants and antipsychotics, are among the most widely prescribed pharmaceuticals of our generation. Psychostimulants find use among our children. Sedatives and hypnotics aid adults in dealing with the day-to-day stress created by our frantic lifestyles. Mood stabilizing agents serve to buffer extreme highs and lows in the emotional cycles of our lives.

Research reported by CNN in 2016 revealed that one in six adults in the U. S. self-report that they are taking prescription mental health medication, with the possibility that numbers may actually be higher.1  The use prevalence of these psychoactive medications creates a need for awareness among health professionals concerning the basics related to psychopharmacology, the medications for the mind.

In Your Head

Medications whose stated purpose is to alter the chemical balance in the brain and central nervous system (CNS) are in wide, ever increasing, use. The treatment of mental illness symptoms, mood disturbance, and even inability to focus attention all employ prescription substances that affect the function of the mind. Pharmaceuticals designed to alter brain chemistry are as a general grouping referred to as psychopharmacology medications, although terms ranging from neuropsychopharmacology to just plain “psych meds” are used as general identifiers for the group.

Psychopharmacology medications fall into loose categories based on the chemistry of how they work in our body as well as their primary effect on the central nervous system. Some medications used in psychiatric care have effect in more than one area. Common groupings are:

  • Antianxiety Agents
  • Antidepressants
  • Antipsychotics
  • Mood Stabilizers
  • Psychostimulants

Each of the medications that fall into these loose groupings possesses the ability to influence or affect the chemistry within the brain. Special emphasis has been placed on the role that brain chemicals known as neurotransmitters play due to recent insights into the cellular structure of key brain cells and the critical function these chemical messengers play.

Neurotransmitters

Neurotransmitters such as dopamine and serotonin are manufactured in nerve cells known as neurons for the purpose of conveying messages from cell to cell across a tiny physical space between adjacent nerve cells known as the synaptic gap. The nerve cell structure sending the message, called the axon, exudes messenger chemicals, neurotransmitters, towards the receiving structure, a dendrite, on the next nerve cell of a message chain, neural pathway. The surface of the receiving dendrite is covered with specialized proteins that act as receptor sites for messenger chemicals. Receptor sites have special characteristics that respond to the unique shape of each specific neurotransmitter, much as the lock on your front door responds only to the unique shape of the key in your hand. Once a neurotransmitter is received into a corresponding receptor site the chemical messenger is either destroyed or reabsorbed and taken out of circulation. ?
neurotransmitters

Be aware that manipulation of neurochemicals is quite tricky. Many neurotransmitters have multiple messages they can convey, depending on factors such as which area of the nervous system they are released into as well as what quantities and combinations are present.

Changes in neurotransmitter structure, alterations in the amount of neurotransmitter available to be received or the number of available receptor sites for a particular neurotransmitter all affect the message being sent. Results of a change in neurotransmitter balance or availability may affect thoughts, emotions, behaviors, and mental processes.

The total number of distinct neurotransmitters used within the central nervous system is not known. Over a hundred information carrying molecules have already been discovered, each of which has an important, if often times mysterious, role to play. Only a few of these chemical couriers are currently amiable to direct pharmaceutical manipulation, generally by boosting or suppressing their functional availability. However, those that can be accessed allow new treatment mechanisms and new tools to ease the undesired symptoms found in the behavioral, mental or emotional realms.2

Select Neurotransmitter Function2,3
Acetylcholine
(ACh)
Acetylcholine was the first neurotransmitter recognized, in 1921, for the role it plays, and resulted in a Nobel Prize.
It stimulates muscles, aids in sensory function, facilitates REM sleep, attention, motivation, learning, and memory. Too much ACh can lead to muscle spasms, tremors, and movement disorders. Insufficient ACh leads to a state of torpor or paralysis.
Dopamine Dopamine is strongly associated with brain reward mechanisms, arousal, and general physical motivation. If a feeling of anticipation is present proceeding an action, activity or consuming a substance, dopamine is likely involved.
Too much dopamine has been associated with Schizophrenia, while too little accompanies Parkinson’s disease and social anxiety disorders.
Endorphins
(enkephalins)
Endorphins are a group of very similar neurochemicals. Every runner has heard of endorphins. They function similarly to opioid narcotics. Their presence reduces pain perception and effects pleasure, they tend to reduce stress, and enhance calm feelings.
GABA
(gamma aminobutyric acid)
GABA slows the excitation that leads to anxiety. Its presence has been linked to sleep and eating disorders. Too little GABA is associated with anxiety disorders and even epilepsy.
Glutamate Glutamate is the most common neurotransmitter in the CNS, and is very important to memory function as well as how pain is perceived. Excess glutamate is associated with the destruction of brain cells, such as in ALS/ Lou Gehrig’s disease.
Norepinephrine
(noradrenalin)
Norepinephrine also won its discoverer a Nobel Prize.
This is the “high alert” transmitter, increasing heart rate and blood pressure to deal with stress or danger. It prompts both physical and mental arousal, and can elevate the mood. It is also important for forming lasting memories.
Serotonin The link between serotonin and mood has been widely discussed. Not enough serotonin accompanies depression, excessive carbohydrate cravings, sleep troubles, anger control issues, migraines, irritable bowel syndrome, fibromyalgia, obsessive-compulsive disorder, and an increase in suicide related thoughts and acts.

Psychiatric medications are not like antibiotics. Medications alone seldom result in a permanent “cure” for mental, behavioral or emotional troubles. The goal of psychopharmacology is to help regain proper balance in the chemistry of the brain and restore optimal functioning. The use of medications for the mind is, therefore, in most instances, directed towards the control of symptoms. Controlling symptoms means in effect 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.

Antianxiety Agents

The most commonly diagnosed psychiatric disorders are anxiety disorders which possess a lifetime incidence among adults in the United States of 28.8%.4 The number of prescriptions written for antianxiety agents tripled from 1996 to 2013, a significant increase.5

Medications that affect brain chemistry in such a manner that they lessen or alleviate the sensations of anxiety, worry, stress or fear are known by the term antianxiety agents. These chemicals may also be referred to by terms such as anxiolytics, sedatives, sedative-hypnotics, or minor tranquilizers. Prescription sleep aids are so closely related to antianxiety medications that they are firmly in the realm of psychopharmacological study and use. Barbiturates and benzodiazepines, along with a loose assortment of other prescription chemicals traditionally form the antianxiety group. In recent years, however, barbiturates have fallen from common use in areas other than induction of anesthesia leaving the benzodiazepine subgroup as the mainstay anxiolytic.

Sedatives vs. Hypnotics
Sedative - a sedative lowers excitement and calms the awake patient Hypnotic - a hypnotic produces drowsiness and promotes sleep
Sedatives and Hypnotics are by tradition categorized into a single class because of their common ability to induce a state resembling relaxation, sedation and sleep.

Antianxiety medication can be very useful in treating the symptoms that accompany anxiety disorders and often find use in combination with other forms of treatment, such as cognitive-behavioral therapy. The use of anxiolytics helps to ease symptoms so that non-medication based primary therapy can focus on uncomfortable underlying causations and move forward.

It is important to remember that in the treatment of mood, memory or cognitive function, individualization of care requires selection of the best pharmacologic agent for that person. Due to the type of effects, both primary and secondary, that psychiatric medications have on brain chemistry the best fit in treating a particular person for anxiety will not always be an“antianxiety”medication.

Benzodiazepines

The family of medications known as the benzodiazepines is the heart of anxiolytic, or antianxiety treatment. Benzodiazepines are not a cure for anxiety. Their purpose is that of short-term, symptomatic, adjunctive treatment while other lasting solutions are sought for the core issues creating the anxiety.

Psychiatric Reasons to Consider Using Antianxiety Agents
  • Generalized Anxiety Disorder 
  • Social Phobia
  • Acute Stress Disorder
  • Posttraumatic Stress Disorder
  • Panic Disorder
  • Insomnia
  • Agitation
  • Substance Withdrawal

Benzodiazepine-Related Medications

The recent development of new medications, which seem to act on brain benzodiazepine receptor sites without being true benzodiazepine chemicals opens another path of future treatment of anxiety. The FDA currently approves three benzodiazepine-related medications (zolpidem, zaleplon, eszopiclone) for the treatment of insomnia.

Buspirone

Buspirone (Buspar) is a dopamine (D2 receptor) blocking medication approved for use by the FDA for the treatment of generalized anxiety disorder. Structurally different from the benzodiazepines, buspirone can be used for long periods with no potential for abuse, dependence, or tolerance.6 What buspirone lacks is the quick onset associated with many of the other antianxiety medications. Several weeks of daily dosing is required to achieve anxiolytic benefits.

Anxiolytic Neurophysiology

Gamma-aminobutyric acid (GABA) is a key neurotransmitter associated with anxiety. Medications such as the benzodiazepines (e.g. Valium, Ativan, etc.) and the barbiturates interact with the availability or reception of GABA in the central nervous system. Benzodiazepine medications bind to neurotransmitter receptor sites BZ1 and BZ2 (benzodiazepine receptor sites 1, and 2) and potentiate the effects of GABA. BZ1 is thought to be closely associated with sleep function, while BZ2 influences cognitive, sensory, motor and memory abilities.

In general, benzodiazepines are considered equally effective. Drug choice should be based on individual concerns such as how long it takes to reach effect and how long the effect is desired.

Benzodiazepine Antianxiety Medications6,7
Name (Generic) Brand Name Onset (Oral) Duration
Alprazolam Xanax Intermediate Intermediate
Chlordiazepoxide Librium Intermediate Long
Clonazepam Klonopin Fast Long
Clorazepate Tranxene Fast Long
Diazepam Valium Fast Long
Halazepam Paxipam Intermediate Long
Lorazepam Ativan Intermediate Short
Oxazepam Serax Slow Short
Prazepam Centrax Slow Long
Benzodiazepine Medications Used for Insomnia
Flurazepam Dalmane Intermediate Long
Quazepam Doral Fast Long
Temazepam Restoril Intermediate Short
Triazolam Halcion Intermediate Short
Benzodiazepine-Related Medications
Eszopiclone Lunesta Very Fast Short
Zaleplon Sonata Very Fast Short
Zolpidem Ambien Very Fast Short

Antidepressants

Pharmacologic agents that affect the brain chemistry in such a way as to lifts mood or diminish the symptoms of depression are known by the term antidepressant. Clinical depression is widely believed to be the result of a functional imbalance in the endogenous neurotransmitters of the brain associated with mood (e.g. serotonin, dopamine, and norepinephrine).

The reasons for such imbalance may be on the supply side (i.e. not enough of the correct neurotransmitter is being made), or it may originate on the receiving side (not enough specific receptor sites are available). There may be some unanticipated factor interfering with the function of the neurochemical message system such as malformation of the neurotransmitter molecule, blockage by a third-party neurochemical or pseudo-neurochemical, etc. In most instances, the exact cause is never known, creating the neurohormonal imbalance which results in a given individual's depression. What is known is that when one antidepressive agent fails, there are options that include antidepressants that work by different mechanisms.

Several classes of antidepressant medication exist, grouped together by the neurotransmitter(s) they primarily affect. Antidepressant groupings include;

  • Monoamine Oxidase Inhibitors
  • Norepinephrine-Dopamine Reuptake Inhibitor
  • Selective Serotonin Reuptake Inhibitors
  • Serotonin Dopamine Activity Modulators
  • Serotonin Modulators
  • Serotonin Norepinephrine Reuptake Inhibitor
  • Tricyclic Agents

Antidepressants do not work overnight and may not work at all. In a large study by the British Royal College of Psychiatrists, those clients on antidepressants for three months showed only 50 to 60 percent reporting significant improvement.8 Other studies have shown that around half of clients prescribed antidepressants have no true benefit and many who do have a therapeutic response end up stopping the medicine due to undesired effects.9

Biochemical availability of the pharmacologic agent may occur within hours after taking the first dose. It may, however, take weeks before the positive effect of an antidepressant is apparent. One theory as to why there is a delay of symptom relief is that complex changes must occur within neurotransmitter receptor sites in the brain before significant symptomatic change may be observed. The belief is that the presence of antidepressant medications promotes change in brain protein production at a cellular level leading to an increase in synaptic plasticity, perhaps even encouraging slow progress toward a physically healthier brain. What it means in the short term is that therapeutic support of the person in depression is essential, given the slow onset of medication effect.

Monoamine Oxidase Inhibitors

Neurotransmitters chemically tend to be monoamines. Monoamine oxidase is an enzyme that breaks down neurochemicals such as serotonin, dopamine, and norepinephrine. Medication that inhibits the degradation of these neurotransmitters promotes higher levels of mood by increasing the quantity of available neuroactive chemicals.

MAOIs, as monoamine oxidase inhibitors are commonly referred to, were the first class of antidepressants to see clinical use, following their discovery in 1952. 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.

Monoamine Oxidase Inhibitor Interactions8,10

Food Interactions (Tyramine containing foods)

Drug Interactions
  • Aged cheese
  • Aged, smoked, or pickled meats
  • Yeast extracts
  • Wine (red more than white)
  • Beer
  • Avocado
  • Sauerkraut
  • Caffeine
  • Chocolate
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Meperidine
  • Dextromethorphan
  • Sertraline
  • Sumatriptan
  • Linezolid
  • All serotonergic agents
Interaction symptoms are similar and represent the effects of excessive catecholamine neurotransmitters in the body: Hypertension, Tachycardia, Tremors, Hyperthermia, and Seizures. 

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 for whom they prescribe MAOIs. The client must be able to understand potential risks and follow a very strict, low-tyramine diet.

MAOIs are very useful in the treatment of “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.10

Monoamine Oxidase Inhibitors10
Name (Generic) Brand Name

Elimination Half-life

(hours)
Dietary Restrictions
Phenelzine Nardil 1.5-4 Yes
Tranylcypromine Parnate 1.5-4 Yes

Selegiline

(transdermal patch)
Emsam 1.2 No – however, caution advised if exceeding recommended dosages

Norepinephrine Dopamine Reuptake Inhibitors

Bupropion is an antidepressant distinctly different from the others. 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. Bupropion was withdrawn from the market for a short time in the mid-1980’s subsequent to reports of a slightly higher incidence of seizures amongst bulimia clients. In 1989, bupropion returned to the market with a warning to avoid use in clients with a history of anorexia, bulimia, or seizure disorders.

Norepinephrine Dopamine Reuptake Inhibitors
Name (Generic) Brand Name Starting dose, mg/day Usual dose, mg/day
Bupropion Wellbutrin 75-150 300-450
Bupropion SR Wellbutrin SR 100 300-400
Bupropion XL Wellbutrin XL 150 300-450

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. The selective serotonin reuptake inhibitors (SSRIs) have the ability to effectively increase the amount of available serotonin within the brain. Increased levels of serotonin tend to occur quickly after initiation of medication therapy. Initial medication response may be seen in about two weeks; however full effect may not be observed for up to eight weeks from initiation of treatment.

Overall efficacy between the SSRIs in relieving depression appears similar. Choice of agent should be determined by matching medication characteristics with individual need. 

Selective Serotonin Reuptake Inhibitors

Name (Generic) Brand Name Starting dose, mg/day Usual dose, mg/day
Citalopram Celexa 10-20 20-60
Escitalopram Lexapro 10 10-20
Fluoxetine Prozac 10-20 20-60
Fluvoxamine Luvox 50 50-300
Paroxetine Paxil 10-20 20-60
Paroxetine CR Paxil CR 12.5-25 25-75
Sertraline Zoloft 50 50-200
Serotonin Dopamine Activity Modulators (SDAMs)
Brexpiprazole Rexulti 10-20 20-60
Aripiprazole Abilify  10-15 10-20
Serotonin Modulators
Nefazodone Serzone, Nefadar 50 300-600
Trazodone Desyrel 50 75-300

Serotonin dopamine activity modulators (SDAMs) are new drugs that tend to play the role of adjunct medication for major depression and schizophrenia treatment. Their somewhat dual nature lends some confusion as to whether they are antipsychotics that also treat depression or antidepressants that can be beneficial in the treatment of schizophrenia.11  Whichever view wins out in the end, what is clear is that SDAMs work as a partial agonist of serotonin (5-HT1A) and dopamine D2 receptors. Placing them in the useful category for antidepressants, particularly in those for whom one antidepressant alone is just not enough.

Serotonin modulators (e.g. nefazodone, trazodone) are similar to SSRIs in effect 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.

In October 2003, the US Food and Drug Administration (FDA) issued a public health advisory concerning antidepressants and a possible increase in the risk of suicidal thinking. The following year FDA advisors suggested that concern was justified particularly in children and adolescents taking SSRIs, and recommended a “black box” warning label for all antidepressants to remind prescribers of the risk of increasing suicidal thinking and behavior. Those following the black box issue note that while a slight decrease in treatment of depression may have resulted, what did not occur was a significant increase in monitoring the of clients treated with antidepressants. ?
Serotonin Syndrome12
Serotonin syndrome is a potentially life-threatening condition associated with increased 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)

Serotonin Norepinephrine Reuptake Inhibitor

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 dopamine reuptake effect. Safety and tolerability of the SNRIs are similar to the SSRIs, although monitoring is warranted for an uncommon sustained rise in blood pressure.

Serotonin Norepinephrine Reuptake Inhibitors13
Name (Generic) Brand Name Starting dose, mg/day Usual dose, mg/day
Desvenlafaxine Pristiq 50 50 (no titration)
Duloxetine Cymbalta 30 60-120
Venlafaxine Effexor 37.5 75-300
Venlafaxine XR Effexor XR 37.5 75-300
Noradrenergic and Specific Serotonergic Antidepressant
Mirtazapine Remeron 15 15-45

Mirtazapine (Remeron) is an antidepressant without a home. It is neither a 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.13

Another odd medication is Milnacipran. This medication is a relatively new SNRI, but with a twist. It is currently approved by the FDA for use in the treatment of fibromyalgia, but not for use in depression.14

Tricyclic Antidepressants

Cyclic antidepressants were discovered in the 1950’s. The first cyclic antidepressants were named “tri”-cyclic because their chemical structure somewhat resembled three interlocked rings when drawn out in scientific notation.8 Several other cyclic formulations have been discovered since the days of the three-ringers; however, tradition carries the name tricyclic forward for the general grouping despite its current descriptive inaccuracy.

Cyclic antidepressants find less common use than the current first-line SSRI and SNRI agents. The lack of use of cyclic antidepressants in part is due to a wider neurotransmitter effect, with more brain chemicals being shifted and a resultant broadening of potential side effect profiles.

Cyclic Antidepressants15
Name (Generic) Brand Name Starting dose, mg/day Usual dose, mg/day
Amitriptyline Elavil 25-50 100-300
Amoxapine Asendin 50 100-400
Clomipramine Anafranil 25 100-250
Desipramine Norpramin 25-50 100-300
Doxepin Adapin, Sinequan 25-50 100-300
Imipramine Tofranil 25-50 100-300
Maprotiline Ludiomil 50 100-225
Nortriptyline Pamelor 25 50-200
Protriptyline Vivactil 10 15-60
Trimipramine Surmontil 25-50 100-300

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.15

Antipsychotics

Antipsychotic medications have been around for more than 60 years. These pharmacologic agents affect many neurotransmitter systems and most often are thought of as a treatment for symptoms of schizophrenia, though they have effect against psychosis irrespective of cause. Depending on the individual, antipsychotics may be of benefit for manic episodes, agitation, delirium, and as augmentation therapy for other psychiatric conditions.

Generally speaking, all antipsychotics are equally effective when given at an adequate dose for a sufficient length of time. Please be aware that with these powerful psychopharmaceuticals there will be a wide range of variability in individual client response and sensitivity to unwanted adverse medication effects. This variability in response and sensitivity means that for practical purposes the most important considerations in choice of antipsychotic agents for use in treatment are;

  • Previous experience that this client has had with antipsychotics
  • Experience that a close relative has had with antipsychotics
  • Side effect profile of individual antipsychotic agents

Antipsychotic medications are divided into three categories. Typical antipsychotics (aka neuroleptics, conventional antipsychotics, major tranquilizers) tend to refer to older “first-generation” drugs. Atypical antipsychotics are comprised of newer “second-generation” agents with a narrower pattern of unwanted effects. Finally, there is Clozapine, a somewhat unusual medication with unique antipsychotic properties which forms a very small group all its own. 

The mechanism of action of antipsychotics is complex. What is shared in common is that all antipsychotic medications interact with the metabolism of the neurotransmitter dopamine, the subtype of dopamine referred to as D2 in particular. Each of the antipsychotics varies in the degree to which D2 is affected. They also vary as to the other neurotransmitters they either boost or inhibit. Serotonin, histamine, glutamate, and GABA, along with other neurotransmitters all play a role in the symptoms of psychosis and schizophrenia. Because of this intricacy of discord in the chemistry of the brain, identifying the best antipsychotic to diminish an individual’s symptoms, which has the least unwanted effects, is something of an art form.  

Both atypical and typical antipsychotics are effective in the management of the positive symptoms of schizophrenia. Atypical drugs have a greater effect on the negative symptoms of schizophrenia.

Positive Symptoms of Schizophrenia Negative Symptoms of Schizophrenia
  • Agitation
  • Tension
  • Insomnia
  • Verbal incomprehensibility
  • Bizarre behavior
  • Hallucinations
  • Delusions
  • Paranoia
  • Social withdrawal
  • Lack of motivation
  • Flat or blunted effect
  • Anhedonia (lack of pleasure)
  • Poor hygiene and grooming
  • Limited spontaneous conversation
  • Poor social skills

Typical Antipsychotics

Older, first-generation drugs remain a valuable resource. They are characterized by good efficacy, however, have a higher incidence of Parkinson’s disease-like neuromuscular symptoms (pseudoparkinsonism) and EPS (extrapyramidal side effects). EPS effects include such things as slow and diminished movements (bradykinesia), tremors, rigidity, subjective and objective restlessness (akathisia). Typical antipsychotics also carry a risk of developing a lasting choreoathetotic (spasmodic irregular) movement disorder known as tardive dyskinesia.

Further unwanted effects common to typical antipsychotics are the elevation of serum prolactin, a risk of a cardiac rhythm effect known as QT prolongation, feelings of sedation, and anticholinergic effects.16

Typical Antipsychotics with Side Effect Profile16
Generic Brand Name Sedation EPS Orthostatic Hypotension Anticholinergic
Chlorpromazine Thorazine High Low High Moderate
Thioridazine Mellaril High Low High High
Mesoridazine Serentil Moderate Moderate High High
Molindone Moban Moderate High Moderate Moderate
Perphenazine Trilafon Low High Moderate Low
Loxapine Loxitane Moderate High Moderate Moderate
Trifluoperazine Stelazine Moderate High Low Low
Thiothixene Navane Low High Low Low
Fluphenazine Prolixin Low Very High Low Low
Haloperidol Haldol Low Very High Very Low Very Low

Atypical Antipsychotics and Clozapine

Second-generation drugs are often the first choice in treatment for psychotic symptoms. They have a lower incidence of unwanted EPS as well as a reduced risk of tardive dyskinesia.17 What they lack, however, is a firm record of superior performance over the older typical antipsychotic agents which brings the realization that for any particular client, newer may not be superior to older. Treatment choices should be based on factors such as individual client response, side effect profile, and cost.

Atypical Antipsychotics Side Effect Profile17
Generic Brand Name Sedation EPS Orthostatic Hypotension Anticholinergic
Aripiprazole Abilify Low Low Low None
Olanzapine Zyprexa Moderate Very Low Low Low
Paliperidone Invega Low Low Moderate Very Low
Risperidone Risperdal Low Low Moderate Very Low
Quetiapine Seroquel Moderate Very Low Low Very Low
Ziprasidone Geodon Very Low Low Low None
Clozapine Side Effect Profile
Clozapine Clozaril Very High Very Low High High

Atypical antipsychotics and clozapine have been associated with an increase in metabolic syndrome (e.g. hyperglycemia, dyslipidemia, and hypertension) as well as an increased risk of new onset diabetes. Weight gain is also a significant issue with atypical agents with clozapine and olanzapine having the greatest reports of increase. 

Clozapine

Clozapine is a stand-alone antipsychotic. It affects the dopamine D2 receptor sites, as do all of the antipsychotic medications. Clozapine is highly prized for its history of good effect on schizophrenic clients whose metabolism resist typical and atypical antipsychotic treatment.

The bad news however, and the reason why clozapine is not a first-line antipsychotic, is not the adverse effects of weight gain and risk of metabolic syndrome. It is the presence of an unusually high risk of agranulocytosis. This abnormally low level of white blood cells in the body (agranulocytosis) occurs in approximately 0.38 percent of those being aggressively monitored, down from between 1 and 2 percent of clients who in the past were less carefully followed.18 Some of this tremendous improvement may be due to the FDA requiring practitioners’ prescribing clozapine to weekly monitor white blood cell counts (WBC) for the first six months, then biweekly for the next six months. After that, WBC checks can be every four weeks for the duration of treatment. Making clozapine a high maintenance medication for client and prescriber.

Mood Stabilizers

Mood stabilizers are medications that buffer the dramatic emotional rollercoaster ride which accompanies bipolar affective disorder as well as other conditions possessing a strong mood component such as schizoaffective, manic, or major depressive syndromes.19 The term mood stabilizer applies to medications that alleviate the intensity or the frequency of depressive, hypomanic, manic or mixed episode swings in clients with bipolar affective disorder (aka manic-depression). Mood stabilizers are the mainstay treatment for acute mania. They are used to induce remission in those individuals experiencing symptoms of hypomania, manic episodes, and aid to stabilize mood swing cycles into a maintenance range closer to what that person’s normal would be.

Lithium and a select group of antiepileptic medications form the mood stabilizer psychopharmacology group. Studies of these agents show similar response rates, of between 50 to 60 percent, in clients with acute mania. Choice of agent, therefore, revolves around previous experience for the client, comorbid medical conditions that are present, and side effect profiles of the drug.

Lithium, in particular, a purified mineral straight from a chemist's table of core elements, has a tricky set of potential unwanted effects, starting with the renal system. Clients with compromised renal function may not be able to excrete lithium efficiently and therefore are at risk for lithium intoxication. Common side effects of lithium therapy include polyuria, loose stools, tremor, cognitive effects such as confusion, and weight gain. Around 10 to 20 percent of clients on lithium therapy develop hypothyroidism. Tremors are so common with lithium use that up to 65 percent of clients will experience them to an extent. Sudden worsening of an existing tremor or sudden appearance of a tremor that had not previously been present can be a sign of impending lithium toxicity.20 Interestingly, recent work with lithium suggests it possesses positive unanticipated effects such as neuroprotection and a significant reduction in suicidal acts for those using it.21

The alternative mood stabilizers are closely related to the antiepileptic medication family, and also require careful monitoring. Carbamazepine, for example, may cause dose-related diplopia (double vision) or ataxia (the inability to coordinate muscle movements). Lamotrigine may cause nausea, skin rash, dizziness, or headache. Valproic acid can cause liver problems, gastrointestinal distress, weight gain, and even alopecia (hair loss). Oxcarbazepine is associated with sodium loss and can cause hyponatremia as well as somnolence, dizziness, nausea, or dizziness.

It is unclear how mood stabilizers work. Current thought is that they are able to alter the ion channels of cell walls in the central nervous system. Many also increase available GABA levels.

Mood Stabilizers21,22
Name (Generic) Brand Name Normal Serum Level Weight Effect
Carbamazepine Epitol, Tegretol 4-12 mcg/mL Neutral
Divalproex sodium Depakote 50-125 mcq/mL Increase
Lamotrigine Lamictal n/a Neutral
Lithium carbonate Eskalith, Lithobid 0.5-1.2mEq Increase
Oxcarbazepine Trileptal n/a Neutral
Valproic acid Depakene 50-125 mcq/mL Increase

 

Case Study:

Harold Jennings is a 43-year-old construction worker. He drove himself to the emergency room after work complaining of an extensive skin rash that had developed over the course of three to four days. He also reports feelings of gastric upset, a lingering headache, and an unusual level of fatigue. Physical inspection shows a large area of reddened, raised tissue on the back of one hand, up the dorsal aspect of the forearm, and a second extensive area of discoloration in the mid-back region showing ruddy coloration and demonstrating the presence of intact raised blisters in the rash area.

Mr. Jennings reports that he has never had an allergic reaction to anything, and has no idea what he might have come in contact with at his latest build site which could cause this. He can provide an extensive list of products and chemicals which he routinely works with on construction sites. None on the list are new to him; he has worked with the same materials for several construction seasons. Neither has he changed laundry products or personal care items such as soap or shampoo in some time.

Mr. Jennings is in physically in good health, receives a yearly physical for insurance purposes and visits his group medical clinic twice a year for checkups related to a chronic manic-depressive disorder that is currently in remission.

On questioning, Mr. Jennings relates that he had a medication change at his last clinic visit, from Lithium to Lamotrigine, due to his concern about weight gain with Lithium, six weeks prior to the skin rash. He does not relate this to the allergic rash due to more than a month’s use without problems, and no problems with Lithium other than a few unwanted pounds. 

Lamotrigine Black Box Warning:

Lamotrigine can cause serious rashes requiring hospitalization and discontinuation of treatment, including Stevens-Johnson syndrome/toxic epidermal necrolysis SJS/TEN), a condition which may cause tissue death and detachment of epidural tissue. SJS/TEN occurs in approximately 0.3% to 0.8% of pediatric patients (2 to 17 years of age) and 0.08% to 0.3% in adults receiving lamotrigine.23

Mr. Jennings immediately had his Lamotrigine discontinued and was admitted for close observation of the rash areas with biopsy of tissue. Tissue biopsy revealed epidermal necrosis with tissue detachment had not occurred and supportive measures were initiated to maintain and speed epidermal healing.

NOTE: Lamotrigine-induced rashes manifest infrequently, and when they do it is generally within two to eight weeks of first starting the medication. Due to the serious nature of Stevens-Johnson Syndrome clients should always be cautioned to be alert for a new skin rash. The presence of which is a serious medical complication needing immediate assessment and treatment.

Psychostimulants

Psychostimulants affect the dopaminergic and noradrenergic neurotransmitter systems, causing the release of catecholamine’s from storage sites at synapses in the central nervous system (CNS). Psychostimulants reduce feelings of fatigue, promote alertness and wakefulness, increase the ability to concentrate, and have possible mood enhancing properties. In current psychiatric practice, their use is largely limited to attention deficit and sleep disturbance disorders such as narcolepsy.

Historically attention deficit hyperactivity disorder (ADHD) and attention deficit disorder (ADD) were believed to be a time-limited condition of childhood that must be diagnosed before the age of twelve to exist.24 Data shows that between 8 to 11 percent of school-age children are affected sufficiently to warrant a diagnosis, and between 40 and 60 percent of these go on to adulthood with significant adult ADHD symptoms.25,26

Treatment for ADHD is beginning to shift from strict pharmacotherapy alone toward changes in the environment and stimulation of individuals both without, or still most common, with medication. Behavioral parent training, behavioral classroom management, and behavioral psychotherapy utilize psychostimulants to suppress symptoms while non-pharmaceutical treatment is employed to handle root issues. It is important therefore to remain aware that psychostimulants continue to be present, and indeed the mainstay first-line treatment for attention deficit conditions both in youth and adults, despite efforts to go non-pharmaceutical.27

Available studies fail to show improvement in school performance in children to whom psychostimulants have been prescribed. However, the use of stimulant medication has, in studies, demonstrated improvement in behavior in all children to whom they are given (e.g. children with ADHD, learning disabilities, depression, and even normal children), not just those with ADHD. Adults report an increase in ability to concentrate while taking prescription psychostimulants.

Psychostimulants27
Name (Generic) Brand Name Used in Children Used in Adults
Dexmethylphenidate Focalin Yes Yes
Methylphenidate Ritalin, Methylin, Metadate, Quillivant, Concerta, Daytrana? Yes Yes
Dextroamphetamine Dexedrine, Dextrostat Yes Yes
Amphetamine Dyanavel, Evekeo Yes Yes
Amphetamine mixed salts Adderall Yes Yes
Lisdexamfetamine Vyvanse Yes Yes
Related Medications
Atomoxetine Strattera Yes Yes

Atomoxetine (Strattera) is a non-stimulant approved for use in children older than six years of age, adolescents, and adults diagnosed with ADHD. It is not a true psychostimulant. Instead, it is more closely related to the SNRI medications. Despite a different mode of action, it has stimulatory effects on the sympathetic nervous system and been well received as a psychotherapy alternative, especially in instances where there exists a potential for abuse in the individual receiving treatment.

Summary

Psychopharmaceutical medications are valuable tools in the treatment of mental illness. Psychiatric medications help control symptoms and are a beneficial adjunct to other forms of therapy. The use of prescription medications alters brain chemistry and function, contributing to the goal of clarity of thought and focus. The prevalence of these helpful and therapeutic medications creates a need for awareness among health professionals concerning the basics related to psychoactive pharmacology, the medications for the mind.

References

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This course is applicable for the following professions:

Advanced Registered Nurse Practitioner (ARNP), Clinical Nurse Specialist (CNS), Licensed Practical Nurse (LPN), Licensed Vocational Nurses (LVN), Registered Nurse (RN)

Topics:

Advance Practice Nurse Pharmacology Credit, CPD: Practice Effectively, Pharmacology, Psychiatric


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