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Week 3: Req Readings: Boland, R., & Verduin, M. L. (2022). Kaplan and Sadock's synopsis of psychiatry (12th ed.). Wolters Kluwer.
- Chapter 5: Schizophrenia NIH: https://www.nimh.nih.gov/funding/clinical-research/practical/stard/allmedicationlevels Some mental health needs can be complex and enduring. Individuals with complex mental health needs often experience significant or persistent mental health challenges that impact their functioning at home, work, school, and in the community. Complexities arise from a myriad of factors, including comorbid medical and psychiatric disorders, intellectual and personality dispositions, and treatment limitations. Treatment-resistant depression is a profoundly complex psychiatric disorder in which an individual does not improve despite the provision of usually effective treatment. Often these outcomes are associated with restricted treatment opportunities and not simply a failed treatment response (Cordner et al., 2020). Management strategies for individuals with complex mental health needs begin with a comprehensive history and assessment and a strong therapeutic alliance. Treatment typically includes both psychotherapy and medication management. Often a multidisciplinary team approach is required to provide holistic and alternative treatment approaches. The psychiatric mental health nurse practitioner (PMHNP) is a key member of the team and plays an important role in evaluating, managing, and instilling hope for clients with the most difficult mental health conditions. Depression Depression is a mood disorder characterized by depressive symptoms that last longer than two weeks. Signs and symptoms of depression include:
- sad or irritable mood
- feelings of hopelessness, worthlessness, or emptiness
- diminished interest in activities
- significant weight or appetite changes
- fatigue, sleep disturbances including difficulty sleeping (insomnia) or sleeping too much
- cognitive changes such as difficulty concentrating, remembering information, or making decisions Though the exact cause is unknown, depression is influenced by genetic and environmental factors. Stressful life events, such as giving birth or experiencing emotional trauma, can contribute to the development of depression.
Labels
- Impaired prefrontal cortex Healthy Cellular Environment Neurotransmitters are chemicals that enable neurons (nerve cells in the brain) to communicate with other neurons. The binding of neurotransmitters to receptors on the surfaces of neurons results in excitatory, inhibitory, or modulatory responses. Here we see a healthy amount of neurotransmitters (dopamine, for example) released into the synaptic cleft, where they bind to their receptor and prompt a healthy signal. An imbalance of specific neurotransmitters, including dopamine, serotonin, and norepinephrine, can influence brain activity and result in depression. Legend
- Neurotransmitter (dopamine) Labels
- Healthy neurotransmitter levels and receptor binding Cellular Mechanism of Depression Research in recent years has linked depression to various neurotransmitter imbalances, including lower levels of dopamine, serotonin, and norepinephrine. Depressed patients often have decreased neurotransmitter activity in the prefrontal cortex (PFC) region of the brain. The prefrontal cortex controls attention, mood, and personality, among other functions. Legend
- Neurotransmitter (dopamine) Labels
- Low neurotransmitter levels and receptor binding
Motor Symptoms
- Motor delay
- Dyscoordination
- EPS, e.g., o Parkinsonism o Dyskinesia Affective Symptoms
- Depression
- Anxiety
- Suicidality Cognition
- Attention
- Working memory
- Verbal memory
- Visual memory
- Executive functioning
- Processing speed
- Social conditioning Negative Symptoms
- Affective flattening
- Alogia
- Anhedonia
- Amotivation
- Asociality Symptoms of Psychosis: Hallucinations: perceptual experiences in the absence of external stimuli Examples of hallucinations include:
- Auditory: hearing things that are not there (may include command hallucinations in which voices direct the client to perform actions, often related to self-harm or violence towards others)
- Visual: seeing things that are not there
- Tactile: feeling sensations in the body in the absence of stimuli
- Olfactory: smelling things that are not there
- Gustatory: tasting things that are not there Delusions: fixed false, irrational beliefs Examples of delusions include:
- Persecution: delusions related to being threatened, victimized, or spied on
- Reference: delusions related to receiving personal messages from tv, radio, or actions of others
- Somatic: delusions related to the body, including illness or the presence of foreign objects (e.g. Sometimes people believe there are objects in their bodies; for example, they might think they are infested with insects.)
- Grandeur: delusions related to beliefs of special abilities or powers
- Control: delusions that actions and thoughts are controlled by others Thought Disorder: impairment in the process of thinking and difficulty organizing thoughts in a logical pattern Examples of thought disorder include:
- incoherent speech
- loose associations
- meaningless words
- perseveration Disorganized behavior: disordered or impaired behavior or communication Examples of disorganized behavior include:
- childlike silliness
- unpredictable agitation
- inappropriate clothing for the weather
- poor hygiene
Independent Living: Cognitive and social impairments, chronic unemployment, and limited disability benefits make independent living exceedingly difficult for clients with schizophrenia. Individuals with schizophrenia often face challenges with the higher-level functional skills necessary to engage in advanced self-care activities such as participating in medical care, managing medications, learning to drive, or using transportation effectively (Chronister et al., 2021). The ability of individuals with schizophrenia to live independently varies widely based on social support in the communities where they reside. Because functional impairments remain even when positive symptoms are well-controlled, most individuals with schizophrenia require disability compensation or are dependent on family for financial support (Chronister et al., 2021). Another issue related to independent living is the availability of housing. Clients with schizophrenia and other serious mental health disabilities may have difficulty finding, securing, or maintaining affordable, accessible stable housing. While permanent supportive housing can be an effective solution for clients with chronic mental health disabilities, funding for such programs is insufficient. Morbidity and Mortality: A diagnosis of schizophrenia is associated with a risk of increased morbidity, premature mortality, and a reduced life expectancy of 10 to 20 years due to poor physical health and chronic comorbid conditions. Negative symptoms such as avolition and apathy contribute to sedentary behavior, reduced physical activity, and poor eating habits which impact the development of obesity and comorbidities such as diabetes, cardiovascular disease, and hypertension (Dalkner et al., 2023). Residential and financial instability creates challenges for clients in accessing care and medication resulting in a cycle of relapse and hospitalization for acute management (Dalkner et al., 2023). In meta- analyses, morbidity and mortality were associated with a variety of factors, including alcohol, tobacco, or other substance use and metabolic syndrome. Common causes of death include suicide, cancer, and cardiovascular disease (Wander, 2020). Impairments Associated with Treatment Some clients experience impairments as a result of the disease process of schizophrenia; others face impairments associated with treatment. Click each tab below to learn more. Adverse Effects (AEs) Antipsychotics work by blocking the action of dopamine. Antipsychotics are the mainstay of schizophrenia treatment and are associated with numerous AEs which can cause distress, reduce quality of life, and lead to nonadherence to treatment. The longer the treatment with antipsychotics, the greater the risk for AEs. If not addressed early, AEs can contribute to chronic health problems, disability, and even death. Extrapyramidal Adverse Effects The primary function of the extrapyramidal system (EPS) is to help coordinate muscle movement. The EPS helps maintain posture and regulates involuntary motor movements. Antipsychotic medications can cause AEs in the EPS due to dopamine blockage or depletion in the basal ganglia.
Akathisia
- The subjective feeling of restlessness with a compelling urge to move
- May include repetitive movements, such as finger tapping, rocking, and crossing/uncrossing legs
- Onset is usually within four weeks of starting or increasing medication (D’Souza & Hooten,
- Management may include discontinuing or reducing the antipsychotic dose, switching to alternative antipsychotics, beta-blockers, benzodiazepines, or anticholinergics. Mirtazapine may be used at a low dose (Patel & Marwaha, 2022). Dystonia
- Involuntary contraction or contortion of muscles
- May be painful and [potentially dangerous if throat muscles are involved
- Typically occurs within 48 hours to five days of exposure
- Management may include discontinuing or reducing the antipsychotic dose or switching to an alternative antipsychotic. Antimuscarinic agents or diphenhydramine may help quickly relieve dystonia within minutes (D’Souza & Hooten, 2021). Drug-Induced Parkinsonism
- Tremor, rigidity, and slowed motor function in the trunk and extremities
- Presents with a mask-like face, stooped posture, and slow, shuffling gait
- Management may include discontinuing or reducing the antipsychotic dose, switching to an alternative antipsychotic, and administering anti-Parkinson agents including amantadine, antimuscarinic agents, dopamine agonists, and levodopa (D’Souza & Hooten, 2021). Tardive Dyskinesia
- Involuntary muscle movements most commonly affect the orofacial and tongue muscles, and less commonly, the muscles in the trunk and extremities
- In some cases, tardive dyskinesia may be irreversible
- Management may include discontinuing or reducing the antipsychotic dose or switching to an alternative antipsychotic. Valbenazine is Food and Drug Administration (FDA) approved for the treatment of tardive dyskinesia (Warren et al., 2022). Discover More Watch this video to learn more about differentiating tardive dyskinesia from drug-induced Parkinsonism and treating the conditions
situation. The provider must identify which risk factors are present and identify interventions to improve adherence. Treatment Nonadherence Client
- History of nonadherence
- Poor insight into the disease process
- Substance use
- Cognitive impairment or developmental disability
- Negative attitude Medication
- Adverse effects
- Continued symptoms Environment
- Lack of social support
- Lack of therapeutic alliance
- Practical difficulties getting or taking medications Society
- Illness stigma
- Stigma related to medication adverse effects Common adverse effects that lead to nonadherence include weight gain, sedation, cognitive problems, sexual dysfunction, and Parkinson-like symptoms. The client’s interpretation of severity drives nonadherence; for some clients, sexual dysfunction may not present distress, but for others, the same adverse effect may cause significant distress. Long-Acting Antipsychotic Medications to Improve Treatment Adherence Long-acting antipsychotic medications (LAIs) may be used to improve medication adherence. LAIs can improve client outcomes, reduce the number of hospitalizations and emergency department visits, and reduce healthcare costs for clients with schizophrenia (Lin et al., 2021), as clients do not have to remember to take daily medication. Typically, LAIs provide a more stable drug plasma level. Although strong evidence supports the use of LAIs to treat clients with chronic schizophrenia, the depot forms of medications are used in less than 10% of clients (Lindenmayer et al., 2020). Barriers to the use of LAIs include logistical issues, including the cost of treatment and availability of staff to provide injections, client perception of LAI, and client aversion to needles (Lindenmayer et al., 2020). Medications available in long-acting depot injections include haloperidol, risperidone, paliperidone, aripiprazole, and olanzapine.
Additional Lesson Switching Antipsychotics: Podcast Lesson: the art of switching antipsychotics Discover More Learn more about Raising the Bar with Schizophrenia Treatment Learn by Applying Talitha Talitha is a 26-year-old who presents to the clinic for a medication refill. At age 19, during her sophomore year of college, Talitha began having auditory hallucinations. She was prescribed olanzapine which helped with symptoms. After 6 months, Talitha stopped taking the medication because she felt well and had a relapse, during which the hallucinations returned, and the “voices” became threatening. Talitha developed paranoid symptoms. She was voluntarily hospitalized and was prescribed risperidone, which helped her symptoms but caused sleep disturbances. She was switched to aripiprazole, and the voices returned. Two years ago, she was restarted on olanzapine monotherapy 15 mg daily and has been adhering to the medication regimen since. Talitha denies substance use or other psychiatric history. During the medication refill appointment, Talitha endorses that she still hears voices, but tries to tune them out and not listen to them, since they have caused so much trouble in the past and they make it difficult for her to concentrate at work. Her speech is clear and her thought processes are logical without unusual content. Her affect appears normal, and she denies other psychiatric symptoms. She endorses a 7-pound weight gain since restarting the olanzapine. Her current body mass index (BMI) is 24.3. Question 1 What is the most likely diagnosis for Talitha at this time?
- schizophrenia; multiple episodes, currently in partial remission (Correct answer)
- schizophrenia; multiple episodes, currently in full remission
- schizophrenia; continuous
- schizophrenia; multiple episodes, currently in acute episode Rationale: The most likely diagnosis for Talitha at this time is schizophrenia; multiple episodes, currently in partial remission. Talitha has a history of auditory hallucinations with a first episode, remission, and relapse, which meets the specifier for multiple episodes (American Psychiatric Association [APA],2022). She endorses residual symptoms of schizophrenia, including auditory hallucinations and impairment of executive function, even with medication therapy, which meets the specifier for partial remission(APA,2022).
Eric Eric is a 37-year-old who presents to the clinic with new symptoms. Past psychiatric history: Eric was diagnosed with schizophrenia at age 22. At that time, he had symptoms of paranoia, auditory hallucinations, avolition, and social withdrawal. He was prescribed aripiprazole 10 mg with good results. Over the past 15 years, his dose has been titrated up to 15 mg daily with mild, tolerable adverse effects. Eric has no history of relapse of symptoms before this point. Eric denies substance use or other psychiatric history. During the appointment, Eric endorses his symptoms have returned. He has begun having auditory hallucinations, and he worries that everyone around him is “out to get him.” Upon further inquiry, Eric states that his dad, with whom he lived, died six months ago and Eric no longer has reliable housing. He tries to remember to take his medications daily, but states “I don’t always have them with me if I wind up crashing on someone’s couch.” Question 1 Which of the following is the most likely diagnosis for Eric at this time?
- schizophrenia; multiple episodes, currently in partial remission
- schizophrenia; first episode, currently in partial remission
- schizophrenia; continuous
- schizophrenia; multiple episodes, currently in acute episode (Correct answer) Rationale: The most likely diagnosis for Eric is schizophrenia; multiple episodes, currently in acute episode. Eric has had a history of auditory hallucinations which resolved. At this time the hallucinations have returned, this is a second acute episode. (APA, 2022). Question 2 Which of the following is the most appropriate pharmacologic management strategy for Eric?
- switch to aripiprazole lauroxil 441 mg intramuscular injection once monthly (Correct answer)
- switch to aripiprazole lauroxil 662 mg intramuscular injection once monthly
- switch to aripiprazole lauroxil 882 mg intramuscular injection once monthly Rationale: The most appropriate pharmacologic management strategy for Eric is to switch to aripiprazole lauroxil 441 mg intramuscular injection once monthly. Eric had good symptom control with aripiprazole, but recent life changes have made it difficult to adhere to medication therapy. Switching to a long-acting injectable is an appropriate management strategy. without concerns of opioid overdose, a potentially life-threatening interaction.
Question 3 Which of the following should be discussed with Eric about using oral aripiprazole after receiving his first injection?
- continue to take oral aripiprazole for 21 days and then discontinue
- continue to take oral aripiprazole for 14 days and then discontinue (Correct answer)
- continue to take oral aripiprazole for 7 days and then discontinue
- discontinue oral aripiprazole immediately Rationale: After the initial injection of aripiprazole lauroxil, the client should continue to take oral medication for 14 days and then discontinue. Question 4 Use the ICD- 10 - CM website to select the most appropriate ICD- 10 - CM code for Eric’s diagnosis. The most appropriate code for Eric is F20.89. Rationale: F20.89 Acute exacerbation of chronic schizophrenia is chosen to reflect the exacerbation. Question 5 Which of the following is the appropriate E/M code for this visit?
- 99214
- 99213
- 99215 (Correct answer)
- 99205
- 99204
- 99203 Rationale: Eric is an established client with one chronic illness with exacerbation. He requires adjustment in prescription drug management; therefore, Eric’s visit qualifies as 99215: established client with a high level of medical decision making.
Rationale: The most appropriate pharmacologic management strategies for Skylar include continuing risperidone 6 mg daily and prescribing valbenazine 40 mg daily. Skylar has had good symptom control with risperidone, but is experiencing symptoms of tardive dyskinesia (TD) as evidenced by their AIMS score of 2; a score of 2 or greater indicates TD. The APA recommends treating moderate to severe TD symptoms associated with antipsychotic therapy with a vesicular monoamine transporter 2 (VMAT2) such as valbenazine Question 3 Use the ICD- 10 - CM website to select the most appropriate ICD- 10 - CM code for Skylar’s diagnosis. The most appropriate codes for Skylar are F20.9 and G24. Rationale: F20.9 Schizophrenia reflects Skylar’s diagnosis that is being treated at today’s visit. On the ICD 10 webpage you will see this synonym for the code: Schizophrenia in remission. G24.09 Other drug induced dystonia corresponds to the new diagnosis- tardive dyskinesia. Question 4 Which of the following is the appropriate E/M code for this visit?
- 99214
- 99213
- 99215 (Correct answer)
- 99205
- 99204
- 99203 Rationale: Skylar is an established client with one chronic illness n a newly diagnosed second chronic illness who needs prescription drug management. The new onset TD warrants additional decision making. Therefore, Skylar’s visit qualifies as 99215: established client with high level medical decision making.
Treatment-Resistant Depression Background Treatment-resistant depression (TRD) is a subset of major depressive disorder and is characterized by a lack of improvement despite the provision of traditional and first-line therapeutic options. Many definitions for TRD exist; however, the commonly used criteria are two or more unsuccessful trials of antidepressant pharmacotherapy (Voineskos et al., 2020). TRD diagnosis may be challenging; differentiating individuals with difficult-to-treat depression from those with depression that is chronic and refractory to treatment is complex. According to Cordner et al. (2020), many factors may lead a provider to mislabel a client as having a treatment-resistant disorder. These factors include overlooking a comorbid psychiatric problem or medical cause, missing a diagnosis, or the inability of a client to endure adequate treatment trials. In these circumstances, the client has not been sufficiently treated and does not warrant a label of a treatment-resistant disorder. There is also debate about whether medications from one class should be trialed before diagnosing TRD. Inaccurate TRD diagnosis can lead to pseudo-resistance in which clients who are prescribed suboptimal medication trials discontinued their medications because of adverse side effects. Discover More Learn more about Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression. Management of TRD Several therapeutic options are used in the management of TRD. Click each tab below to learn more. Nutraceuticals: Omega-3 fatty acids and L-methylfolate are adjunctive treatments that may improve symptoms in clients with TRD (Hoepner et al., 2021). Omega-3 fatty acids are thought to treat depression by decreasing chronic inflammation. L-methylfolate is an active form of folate that crosses the blood-brain barrier and reduces inflammation, reduces loss in gray matter, and helps regulate serotonin, dopamine, and norepinephrine. Other agents associated with improvement in depressant symptoms include zinc, magnesium, and coenzyme Q10 (Hoepner et al., 2021).
Psilocybin-Based Treatment Preliminary data indicates that psilocybin-based treatment may be effective in the treatment of major depressive disorder (MDD) (Gukasyan et al., 2022). Psilocybin is a 5HT2a agonist with cognitive enhancement effects due to the high number of receptors in the cortex. Additional research is needed to evaluate long-term effectiveness and safety. STARD Sequenced Treatment Alternatives to Relieve Depression (STARD) was a collaborative study in 2006 funded by the National Institute of Mental Health (NIMH, n.d.) to examine the treatment of depression in clients where the initially prescribed antidepressant proved inadequate. The STARD study, the largest and longest study ever conducted to evaluate depression treatment efficacy, provided some findings which still guide treatment today (NIMH, 2006). In this study, it was found that one in three persons will achieve remission with the first prescribed antidepressant and that most clients who were labeled treatment resistant failed to receive an adequate medication trial. The STARD study revealed that some clients may experience medication efficacy in the first six weeks of a treatment, however, the full medication benefits may not be evident until 10 or 12 weeks of treatment. Prescribers should work with their clients to assess reasons for inadequate response and increase medications to the maximum dose rather than discontinue a medication prematurely. Clients are more likely to achieve remission with an adequate trial of the first prescribed medication than switching medications, as only 25% of clients respond to a second medication. Discover More Learn more about the STARD study Now, examine the image below to learn more about using a stepwise approach based on the STARD study to manage clients with TRD.
Stepwise Approach to Managing TRD Treatment Decision Process
- Initial Evaluation and Management o Not all depressions are equal o A screening tool is used to assess symptoms and severity o Rule-out medical diagnosis (i.e., hypothyroidism, anemia, etc.) o Assess for comorbidities o Substance abuse o obsessive-compulsive disorder (OCD)/post-traumatic stress disorder (PTSD)/anxiety o Select selective serotonin reuptake inhibitor (SSRI) based on above factors Wait/Reassure - minimum of four weeks
- Adequate Response o Continue presenting treatment
- Inadequate Response o Next steps include: ▪ adherence ▪ barriers (cost, cognition) ▪ repeat depression screen ▪ educate ▪ onset of action/dosing ▪ increasing medication dose ▪ consider adding psychotherapy Wait/Reassure - minimum of two to four weeks
- Adequate Response o Continue presenting treatment
- Inadequate/Partial Response o Medication adherence o Barriers o Repeat depression screen o Increase medication (up to max amount recommended) o Psychotherapy adherence Wait/Reassure - minimum of four weeks
- Not Effective? o Re-evaluate o Switch to different SSRI/serotonin and norepinephrine reuptake inhibitors (SNRI) (remission success of 25 percent)
