Clinical Pearls in Geriatric Psychopharmacology

Last updated: November 30, 2018

Host: Wegdan Rashad, MD

  • Today’s topic is geriatric psychopharmacology.
  • Do one thing at a time. Start low and go slow with medication titration and avoid PRN prescribing. Avoid medications on the Beers list like antihistamines, anticholinergics, and tricyclic antidepressants.
  • In patients with diabetes or those prone to orthostasis, consider ziprasidone or aripiprazole. For glaucoma, consider aripiprazole, risperidone, and quetiapine. For those with Parkinson’s disease, consider low-dose quetiapine or clozapine.
  • The syndrome of inappropriate ADH occurs with SSRI use and is not dose-dependent. Check the serum sodium before the drug is started and at weeks one and two after treatment begins.
  • Lithium is a first line drug for the treatment of acute mania in geriatrics. It is advised to dose it once at night with an immediate acting formulation. Keep serum levels at 0.4 to 0.8 mEq/L.


Hello everyone and welcome to the Psychopharmacology Institute podcast. I’m your host, Dr. Wegdan Rashad. In this series we will be discussing topics that matter to you, the mental health clinician, in your practice, sharing expert opinions and the latest research.

Our topic today is geriatric psychopharmacology. I have worked with senior citizens and certainly, it has been enriching at both the personal and professional level. And one of the lessons I learned is that working with seniors is often a challenge in a fast-paced setting. It requires a good deal of patience, communication and solid knowledge of psychopharmacology.

With the help of snippets from Dr. Sandra Jacobson’s, excellent lecture entitled “Geriatric Psychopharmacology: A Practical Update” we hope to equip you with the clinical pearls for effective prescribing. We will also explore the pharmacokinetic changes that occur with age and touch upon different psychotropic groups in the context of the geriatric population.

Dr. Jacobson is affiliated with the University of Arizona and you can find the full lecture on our website,

So let’s kick off with some starting points on principles of prescribing.

Dr. Jacobson:
Think of each prescription that you write as a clinical experiment for which you need to remove as many confounding factors as possible by first making an accurate diagnosis using standardized criteria, then explicitly listing target symptoms, then objectively rating target symptoms both at baseline and as the trial progresses using numbers if possible, making that baseline psychotropic-free if that’s possible, making only one medication change at a time, documenting the drug dosage and titration schedule in the medical record and documenting side effects and their management. Then once you add notes about drug levels or adherence, you’ll have a complete record of the adequacy of that trial just as you would with a formal clinical drug trial.

So basically, documenting and diligently following up symptoms and side effects. An equally important step is to build an alliance with your patient and their families, and this alliance is based on open and clear communication.

Dr. Jacobson:
Here’s something that surprises many prescribers starting out in geriatrics; once the patient and family leave your office, much of the time, they don’t remember what you said. Always, always put information and instructions in writing. It comes down to if you don’t write it down and hand it to them as they walk out the door, it didn’t happen or it won’t be done. Keep instruction as simple as possible and use once daily dosing whenever you can. Where multiple daily doses are unavoidable, write actual times on the prescription after talking to your patient and their family as to what times would be practical. Include with your written information the reasons the drug is prescribed and expected side effects.

Communication goes a long way. We can also encourage them to use a pill box and medication reminders such as alarm watches to overcome forgetfulness in taking their meds.

Now, for more specific prescribing tips and tricks. First of all, you will need to be familiar with and have handy the Beers list of medications that are inappropriate for use in older adults. This includes medications such as some antihistamines, anticholinergics, tricyclic antidepressants and many more. You will find the link to this list in the references section of our podcast transcript. So that’s one.

Second, you’ll need to know the holy grail of geriatric psychopharm.

Dr. Jacobson:
One of the cardinal rules in geriatrics is to do one thing at a time. Use only one drug if possible. Of course, sometimes two drugs are indicated like an antidepressant and an antipsychotic in a patient with depression with psychotic features.

Another key tip is to start low and go slow.

Dr. Jacobson:
Effective doses of psychotropics for older patients may be one-half to one-third of the usual dose. Dividing the drug dosage can also be helpful in cases where adverse effects are related to peak levels. But as you might expect, adherence or compliance drops rapidly as you move from daily to b.i.d. or t.i.d. dosing.

Another is to avoid PRN prescribing and be sure to document an endpoint of treatment or the next time the patient should return to your clinic for a follow-up.
Wondering why we need to take those precautions? We are about to find out. Stay tuned!

As our bodies grow older our ability to take up and handle drugs changes. Let’s hear Dr. Jacobson’s excellent summary of the pharmacokinetic changes that occur with age.

Dr. Jacobson:
The rate of absorption can be slower with aging and with the use of antacids or bowel medications common in very elderly patients that contain calcium or aluminum. But because the extent of absorption is relatively unaffected by aging at least in the absence of disease.

Distribution is a process that can be significantly affected by aging because as lean body mass decreases, there is a relative, relative increase in fat stores. This is true even for thin elderly individuals. Furthermore, as the half-life of a drug is directly proportional to its volume of distribution, any lipophilic drug will remain in the body longer, that is have a longer half-life, in geriatric compared to younger patients.

In general, oxidation reactions are significantly affected by normal aging, where as glucuronidation actions are not so that medications metabolized through glucuronidation are preferred in geriatrics. In fact, however, only two of the CYP450 enzymes important to psychotropic metabolism have activities that are meaningfully reduced with aging, and that would be CYP1A2 and CYP3A.
Clearance is the major determinant of the steady-state plasma concentration of a drug. P-glycoprotein promotes drug clearance from the liver and the kidneys through its action as an efflux pump, a pump out pump. With aging, not only is pump function reduced but hepatic blood flow and renal clearance also are reduced. Reduced drug clearance is associated with an increased steady-state drug concentration with greater therapeutic and toxic effects. Reduced drug clearance can be offset by a reduction in dosing rate. And this is the reason for the start low and go slow rule in geriatric prescribing.

So in a nutshell, absorption slows down, the half-life is longer, oxidation and drug clearance are reduced.
So, you’re probably thinking, yes pharmacokinetics is cool, but I still don’t have practical tips for real life prescribing. If you’re looking for practical tips, you’ll get practical tips! In the next section, we will run through antipsychotics, antidepressants and mood stabilizer use in older adults.

The FDA has a black box warning for the use of antipsychotics in patients with dementia as it is associated with higher morbidity and mortality risk. However, antipsychotics can still be used in the geriatric population but with some caution.

Dr. Jacobson:
Drug interactions of note for older patients prescribed antipsychotic medications include: First and foremost, a potentially serious interaction of clozapine with benzodiazepines involving cardiorespiratory collapse. This syndrome can be fatal. Beta-blockers commonly used in elderly patients used with antipsychotics can result in increased levels of both classes of drugs. Levodopa which can in combination with antipsychotic have a reduced antiparkinson effect. This excludes two drugs, clozapine, and quetiapine. Clozapine certainly, quetiapine to a lesser extent. Use of antipsychotics with CYP3A4 inhibitors results in increased levels of aripiprazole, pimozide, quetiapine, risperidone and ziprasidone, all metabolized by CYP3A4. Similarly, use of drugs with CYP1A2 inhibitors result in increased levels of clozapine and olanzapine. And finally, drugs that prolong the QTc interval used with mesoridazine, thioridazine or ziprasidone result in additive effects with risk of torsade which can be fatal.

Certainly, it could be useful to have a drug interaction guide with you when prescribing. These are not benign drugs, if you can avoid prescribing antipsychotics altogether in older adults, that would be better. You must weigh the extrapyramidal effects of first-generation antipsychotics against the metabolic effects and high cost of second generation antipsychotics.

Dr. Jacobson:
In elderly patients, comorbid medical conditions often limit or guide choice of antipsychotics. For patients with diabetes, consider the use of ziprasidone and aripiprazole. For patients with glaucoma, avoid drugs that have anticholinergic effects. Consider aripiprazole, risperidone, and quetiapine as preferred drugs. For patients with Parkinson’s disease, consider low-dose quetiapine or even clozapine. For patients with tardive dyskinesia, consider clozapine, olanzapine, quetiapine or aripiprazole.

As you know, antipsychotics are riddled with adverse effects ranging from orthostatic hypotension to metabolic and extrapyramidal side effects, not to mention the FDA black box warning. So, what to about some of those adverse effects?

Dr. Jacobson:
With regards to the adverse effect of orthostatic hypotension, aripiprazole, lurasidone, and ziprasidone have a low affinity for the alpha-1 receptor so are less likely to cause this kind of problem. And orthostasis, in general, can be minimized using small, divided oral doses and titrating slowly. As far as the adverse effect of metabolic syndrome, aripiprazole, asenapine, lurasidone, paliperidone, and ziprasidone confer the least risk. And as far as extrapyramidal effects, quetiapine and iloperidone confer a low risk whereas clozapine is devoid of extrapyramidal effects although clozapine has other important adverse effects including hypotension, sedation, and aspiration.

Aripiprazole is also relatively safe regarding patients at risk for QTc prolongation, but keep an eye on the emergence of akathisia. Also, routine use of anticholinergics to prevent EPS with the use of first generation antipsychotics is a bad idea.

Now, let’s swiftly move to antidepressants!

Dr. Jacobson:
As far as choice of drug, first line drugs for treatment of depression in elders include SSRIs and SNRIs. ECT remains the treatment of choice for elders with melancholic depression with failure to thrive and in those with psychotic depression. Tricyclic antidepressants and non-selective MAOIs are not recommended as safe in elderly patients.

Regarding treatment-resistant depression in the elderly, you can refer to our last podcast released earlier this month which covers the basic grounds for diagnosis and management of treatment-resistant depression.

Dr. Jacobson:
In general, tricyclics are not recommended in geriatrics nor are non-selective MAO inhibitors. SIADH is not dose-dependent. It has a 12 percent incidence with SSRI use and the first sign of it can be a change in mental status. For this reason, when you are using SSRIs in elderly patients, it’s recommended that you check the serum sodium before the drug is started and at weeks one and two after treatment begins. All antidepressant classes are associated with an increased risk of falls, extrapyramidal effects, and akathisia.

So be alert, dear listener, for mental status changes in patients taking SSRIs. OK, so what about bipolar patients? You have a 70-year-old patient with a history of bipolar disorder presenting with mania, what to do? Let’s look at our old friend, lithium.

Dr. Jacobson:
This is a first line drug for the treatment of acute mania in geriatrics and this is despite concerns about renal effects and toxicity with rapid dose escalation. Clearance of the drug lithium is directly proportional to GFR. You are advised to dose this drug in the elderly on a once nightly basis with an immediate acting formulation to allow the kidneys time to recover before the next nightly dose. Serum levels are checked seven days after a dose change from eight to 12 hours after the last dose. That is a trough level. In geriatrics, lithium serum levels are kept on the low side between 0.4 and 0.8 mEq/L even for the treatment of acute mania. This is so despite a poor correlation of serum levels with brain levels in elders.

So, overall let’s keep the serum lithium level between 0.4 and 0.8 mEq/L. What about the other mood stabilizers?

Dr. Jacobson:
For valproate, the extended-release formulation, Depakote ER and sprinkles, provide steadier serum levels with reduced peak level side effects. For lamotrigine, the long titration period in elderly patients limits its value as monotherapy but it can be very useful used early in combination therapy.

Congratulations for reaching this far! Now for our final psychopharm nugget. You may very well encounter an older adult who complains of insomnia. My colleague, Dr. Dana Wang had an interview with Dr. Jacobson and asked her about that in particular.

Dr. Wang:
Aside from non-pharmacological interventions such as sleep hygiene and CBT for insomnia, what are your go-to medications to treat geriatric insomnia, as this is
such a common problem?

Dr. Jacobson:
So with regard to insomnia when I have to use a drug, my favorites are, in order, trazodone still 25 to 50 mg. Gabapentin used according to a silly mnemonic that we have called the 1, 2, 3 punch and that is on night one, the patient is given 100 mg. If they sleep at 100 mg, that’s their dose. On night two, they’re given 200 mg. If they sleep at that dose, then that dose is continued. And on night three, 300 mg. So it’s just a way to figure out what’s the right dose for that patient. And then the third medication that I like to use is mirtazapine. And this is at a very low dose, much better for sedative effect at 3.75 to 7.5 mg.
Now, melatonin deserves a commentary. It’s not one of my choices but I want to say a couple of things about it. Melatonin is used widely. If you ask your patients about it, you will find that many of them have tried this as a sleeper. It is not actually a hypnotic and the doses that are sold over the counter are very large. There are orders of magnitude larger than might be appropriate even for non-elderly patients. Melatonin does have a role in the treatment of sleep disturbances but that role is in resetting a circadian clock disturbance providing a cue to fall asleep at a desired time. It works actually kind of poorly to maintain sleep overnight.

Dr. Wang covers interesting and modern issues in geriatric psychopharmacology in this interview, so, make sure to hear the full interview, available for our premium members.

And that about concludes our pearls to geriatric psychopharm. Only one thing left… yes, that’s right: the key points!

Key Points

  • Documenting dosage, titration, adverse effects and duration of treatment is important. Also, ensure that you give patient instructions in clear and dare I say, legible writing.
  • Do one thing at a time. Start low and go slow with medication titration and avoid PRN prescribing. Avoid medications on the Beers list like antihistamines, anticholinergics, and tricyclic antidepressants.
  • With age, absorption slows down, the half-life is longer, oxidation and clearance of drugs are reduced. Glucuronidation is not very affected with age.
  • In patients with diabetes or those prone to orthostasis, consider ziprasidone or aripiprazole. For patients with glaucoma, consider aripiprazole, risperidone, and quetiapine. For those with Parkinson’s disease, consider low-dose quetiapine or clozapine.
  • The syndrome of inappropriate ADH occurs with SSRI use and is not dose dependent. Check the serum sodium before the drug is started and at weeks one and two after treatment begins.
  • Lithium is a first line drug for the treatment of acute mania in geriatrics. It is advised to dose it once at night with an immediate-acting formulation. Keep serum levels at 0.4 to 0.8 mEq/L.
  • Try non-pharmacological strategies for insomnia first and if it fails you can try trazodone, gabapentin and low doses mirtazapine.

Liked our podcast? Visit us at where you can find more podcasts and some lectures absolutely free. You can choose to become a premium member to access all lectures and interviews. Also, we would be thrilled to hear from you, drop us an email at

The following people participated in this episode: Dr. Flavio Guzman as the general editor, Rosario Anon Suarez as the audio engineer, Pamela Gonzalez as the project manager and myself, Dr. Wegdan Rashad as the host. We’d also like to thank Dr. Sandra Jacobson and Dr. Dana Wang, for being with us.

Thank you for joining us in today’s podcast until the next episode, goodbye!


  1. American Geriatrics Society 2015 Beers Criteria Update Expert Panel, Fick, D. M., Semla, T. P., Beizer, J., Brandt, N., Dombrowski, R., … & Giovannetti, E. (2015). American Geriatrics Society 2015 updated beers criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society, 63(11), 2227-2246.

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