PAC 610 Module 4 Antipsychotics and Mood Stabilizers Example

Trade-Offs in Every Bottle: Antipsychotics, Lithium and Two Clients at an Outpatient Program

Student Name

Psychology and Addiction Studies Program, Aspen University

PAC 610: Psychopharmacology

Instructor Name

Month Day, Year

Trade-Offs in Every Bottle: Antipsychotics, Lithium and Two Clients at an Outpatient Program

A pair of Ridgeview Recovery Center clients, from the same invented Knoxville program, illustrate the dilemmas of this module. Marcus, twenty-six, has schizophrenia and a cannabis use disorder and has gained about twenty pounds in the six months since starting olanzapine. He says he would rather hear voices than look like this. Renee, forty-one, has bipolar I disorder and an alcohol use disorder and has been stable on lithium for three years; her counselor has learned that on hot summer weekends she spends long hours outdoors drinking beer. Both clients take medications that help them and can also harm them.

How Antipsychotics Act

All antipsychotics block dopamine D2 receptors to some degree, and this is thought to reduce psychotic symptoms such as hallucinations and delusions. First-generation drugs such as haloperidol block D2 receptors strongly, which also produces movement side effects, including stiffness, restlessness and, with long use, involuntary movements called tardive dyskinesia. Second-generation drugs such as olanzapine, risperidone, quetiapine and aripiprazole also act on serotonin and other receptors. They generally cause fewer movement problems, but several cause weight gain, raised blood sugar and abnormal cholesterol.

Comparing Antipsychotics

Leucht et al. (2013) compared 15 antipsychotics in a multiple-treatments meta-analysis of 212 trials with more than 43,000 participants with schizophrenia. All were more effective than placebo. Clozapine was the most effective, followed by amisulpride, olanzapine and risperidone, but the differences in effectiveness among most drugs were small. The differences in side effects were large. Olanzapine and zotepine caused the most weight gain, haloperidol the most movement side effects and clozapine the most sedation. The authors argued that the old division into first and second generations was too crude and that drug choice should be fitted to each patient's priorities and vulnerabilities.

What Happens in Real Use

Lieberman et al. (2005) reported the CATIE trial, which randomly assigned about 1,500 people with chronic schizophrenia to one of several antipsychotics and followed them for up to 18 months. The main outcome was simply how long patients kept taking the assigned drug. About three quarters stopped before 18 months, because the drug did not work well enough, because of side effects or because they chose to. Patients on olanzapine stayed on it longest, but olanzapine also produced the most weight gain and the largest rises in blood sugar and cholesterol. The older drug in the trial, perphenazine, did about as well as most of the newer ones. For counselors, CATIE's lesson is that most people stop their antipsychotic sooner or later, often because of how it makes them feel.

Lithium and Other Mood Stabilizers

Lithium has been used for bipolar disorder for decades. Geddes et al. (2004) reviewed randomized trials of long-term lithium against placebo and found that lithium reduced the risk of any relapse by about a third and the risk of manic relapse by a similar amount, with a smaller and less certain effect on depressive relapse. Cipriani et al. (2013) reviewed trials of lithium in mood disorders and found that it reduced the number of suicides and deaths from all causes compared with placebo, an effect not clearly shown for other mood stabilizers.

Lithium's drawback is its narrow margin between a helpful and a toxic level. It is removed by the kidneys, and anything that reduces fluid or affects kidney handling can raise the level: dehydration from heat, vomiting or diarrhea, heavy drinking, low-salt diets and common drugs such as ibuprofen and some blood pressure medications. Early signs of toxicity include nausea, diarrhea, a coarse tremor, unsteadiness and confusion; severe toxicity is a medical emergency. Regular blood tests monitor the level and kidney and thyroid function. Other mood stabilizers include valproate, lamotrigine and carbamazepine, along with several second-generation antipsychotics, each with its own risks.

Monitoring Over Time

Because many antipsychotics affect weight, blood sugar and cholesterol, people taking them need regular checks of weight, waist size, blood pressure, glucose and lipids, especially in the first months. Those on clozapine need regular blood counts because of a rare but serious drop in white blood cells. People on lithium need regular level checks and tests of kidney and thyroid function. Counselors see clients more often than prescribers do and are well placed to notice changes such as new tremor, unusual sleepiness or rapid weight gain between appointments.

Applying the Evidence to Marcus

Marcus's weight gain is a known effect of olanzapine, and Leucht and colleagues' comparison shows that other drugs carry less risk of it, though they may be somewhat less effective or bring other side effects. His cannabis use matters too, since heavy cannabis use is associated with worse psychotic symptoms. His counselor's role is not to recommend a drug but to take his concern seriously, explain that there are options with different trade-offs and help him raise it with his prescriber rather than stop on his own. Abruptly stopping an antipsychotic carries a high risk of relapse. Counseling can also support exercise and diet changes, which help with weight gain whichever drug he takes.

Applying the Evidence to Renee

Renee's situation is a safety concern. Heat, sweating and drinking can all lead to dehydration, which can raise her lithium level. Her counselor should make sure Renee knows the early signs of toxicity and what to do if they appear, encourage her to drink water during hot weather and, with her consent, tell her prescriber about the weekend drinking so that her levels can be checked. The alcohol use also deserves attention in its own right, as it can destabilize mood and interfere with treatment. Lithium's protective effect against suicide, shown by Cipriani and colleagues, is a strong reason to help her stay on it safely rather than stop.

Conclusion

Antipsychotics and mood stabilizers help many people, but every choice trades one set of risks for another. Leucht and colleagues show that antipsychotics differ more in side effects than in benefit, and CATIE shows that most patients stop their drug within 18 months. Lithium prevents relapse and suicide but requires careful attention to hydration and interacting drugs. Counselors who understand these trade-offs can help clients voice their concerns, notice warning signs and stay connected to their prescribers.

References

Cipriani, A., Hawton, K., Stockton, S., & Geddes, J. R. (2013). Lithium in the prevention of suicide in mood disorders: Updated systematic review and meta-analysis. BMJ, 346, Article f3646. https://doi.org/10.1136/bmj.f3646

Geddes, J. R., Burgess, S., Hawton, K., Jamison, K., & Goodwin, G. M. (2004). Long-term lithium therapy for bipolar disorder: Systematic review and meta-analysis of randomized controlled trials. American Journal of Psychiatry, 161(2), 217-222. https://doi.org/10.1176/appi.ajp.161.2.217

Leucht, S., Cipriani, A., Spineli, L., Mavridis, D., Örey, D., Richter, F., Samara, M., Barbui, C., Engel, R. R., Geddes, J. R., Kissling, W., Stapf, M. P., Lässig, B., Salanti, G., & Davis, J. M. (2013). Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: A multiple-treatments meta-analysis. The Lancet, 382(9896), 951-962. https://doi.org/10.1016/S0140-6736(13)60733-3

Lieberman, J. A., Stroup, T. S., McEvoy, J. P., Swartz, M. S., Rosenheck, R. A., Perkins, D. O., Keefe, R. S. E., Davis, S. M., Davis, C. E., Lebowitz, B. D., Severe, J., & Hsiao, J. K. (2005). Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. New England Journal of Medicine, 353(12), 1209-1223. https://doi.org/10.1056/NEJMoa051688