Tag: psychosis

The Real Story Behind Using Two Antipsychotics For Schizophrenia

It wasn’t that long ago when I was sitting in lectures as a first-year psychiatry resident. I learned about the first- and second-generation antipsychotic medications in detail. One commandment that was always preached in my training was to never combine two antipsychotic medications because there is no additional benefit. Today we are here to explore this idea and see if there is truly no additional benefit to using two antipsychotics and explore why there is so much antipsychotic polypharmacy in serious mental illness.  

Introduction

While all training programs preach the use of mono-therapy when it comes to the use of antipsychotics in clinical practice, the reality is up to 50% of psychiatric inpatients are receiving antipsychotic polypharmacy. 

Since most guidelines discourage the use of multiple antipsychotic medications, why are many psychiatrists going against these guidelines? In most cases we are just trying to stabilize patients, get them better, and keep them out of the hospital as the goal is to provide most psychiatric care in the community. To reach these goals a single medication does not always produce the desired results. 

Patients that end up on multiple antipsychotics have some unique characteristics. They tend to have more severe psychotic symptoms, are male, unemployed, and younger. Those with frequent inpatient admissions on involuntary status are also more likely to end up on two medications. 

What To Do When a Single Medication Is Not Enough?

The use of multiple antipsychotics is an area of limitted research. However, there is a difference between rational polypharmacy and irrational polypharmacy.

We should start this discussion by saying a patient should be started on monotherapy titrated to an effective dose and continued on the medication for 6 weeks prior to making a change. If the first medications fails, then switching to another medication or long acting injectable is a reasonable next step. If after another 6 weeks of treatment the patient remains unstable and symptomatic the technical next step is to start clozapine. There are many reasons why clozapine may not be a good option for a particular patient including the strict requirements for weekly complete blood cell counts CBCs.

Assuming this process is followed and the patient is still symptomatic what’s the next step?

Consider Receptor Binding Profiles

This is the first step in prescribing two medications rationally. Most first-generation medications such as Haldol will bind tightly to D2 receptors and stay bound to the sites longer. Second-generation medications like quetiapine are known to bind to the receptors and quickly dissociate giving an on-off like effect. Tight binding and longer duration of binding can lead to extrapyramidal side effects (EPS), whereas quick on-off medications like quetiapine have limitted EPS risk. 

You should also consider other receptors the medication may target such as histamine and muscarinic cholinergic receptors. It would be best to avoid combining two medications that have high antihistamine and anticholinergic activity.

Let’s look at some scenarios where antipsychotic polypharmacy makes sense. 

Patients With Acute Agitation

This is a common problem on the inpatient unit. A patient is on a low-potency quick on-off medication like quetiapine but remains symptomatic and is engaging in dangerous behavior. 

The addition of a higher potency, higher affinity medication like Haldol makes some sense here. This will control the acute agitation, can be titrated until the psychotic aggression is controlled, and can be stopped as soon as the patient is stable on quetiapine. We can see how the receptor binding profile makes this combination reasonable.

Clozapine Refractory Patients

What do you do when a patient is on the best antipsychotic medication but remains symptomatic? 

We do have several lines of evidence that we can look at for this question. One option is to add low dose risperidone. This is a similar idea to adding Haldol to quetiapine. Clozapine has lower affinity for the D2 receptor than risperidone which has much higher affinity for D2 receptors. There were two placebo-controlled trials that support this combination. Before combining medications, I would suggest obtaining a clozapine level to make sure it’s therapeutic. 

There are two more recent studies that compared multiple antipsychotic medication combinations and used rehospitalization as a measure of effectiveness. Both studies found a significant reduction in rehospitalization for patients receiving polypharmacy compared to those receiving monotherapy. The best outcome was achieved when clozapine was combined with aripiprazole. 

Patient is On a Long Acting Injectable (LAI) but Remains Symptomatic at the Highest Dose 

This is a common problem because the doses of LAIs are limitted. For example, the LAI aripiprazole (Aristida) is limitted to a maximum dose of 20 mg/day. The oral formulations of aripiprazole allow for a maximum dose of 30 mg/day. One strategy is to give the injection early. This will usually be done on week 3 for formulations that last 4 weeks. Another option is to add another medication with a different receptor binding profile such as the clozapine aripiprazole combination that was shown to reduce the risk of rehospitalization.

Treatment of Insomnia 

The addition of low dose quetiapine to a medication like paliperidone is common in clinical practice. Once D2 receptor blockade has been maximized by reaching an effective dose of paliperidone, considering the addition of as need (PRN) quetiapine for its low potency and sedating properties is reasonable. The medication should be used PRN only and should be removed once the insomnia has resolved. Consider a sleep study if sleep apnea is possible and using other options such as short-term orexin antagonists, melatonin, and sedating antidepressant if appropriate. 

Treatment of Antipsychotic Induced Side Effects 

I know what you are going to say, adding a medication to treat a side effect of another medication doesn’t make sense. Let’s take an example to illustrate why this makes sense. If a patient is stable on risperidone and is discovered to have an elevated prolactin level you have an obligation to address it. The addition of low dose aripiprazole has been proven to reduce prolactin levels in these cases. Another possibility is using aripiprazole to reduce the metabolic burden of medications such as clozapine. There is much more limited data in this area and I would consider metformin a much better option to start with if antipsychotic induced weight gain is a problem.

In the process of Switching Medication the Patient Achieves Remission 

This is another common clinical scenario. A patient didn’t respond to a medication, and you begin decreasing the dose of the first medication while titrating the new medicine. Then suddenly they are better. You don’t know why but they are better than they have ever been and now you are afraid to make any additional changes. Ideally you would finish the process and appropriately titrate the new medicine while discontinuing the ineffective medication. There is no good data to support inadequate dosing of two antipsychotics, and it’s best to continue your taper/titration and reevaluate after it’s complete.

Conclusion

There is still limited data to support the use of multiple antipsychotic medications although it is often seen in clinical practice. There are a few places where the addition of a second medication makes sense, and we can use receptor profiles to help us make rational decisions and avoid excess side effect burden. 

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Hey Doc, What’s Psychogenic Polydipsia?

This is one of the interesting occurrences that can present on the medical floors, emergency rooms, or inpatient units. 

A patient comes in with an established diagnosis of schizophrenia and is currently taking ziprasidone. The person is constantly asking for glasses of water and drinking water excessively throughout the day. 

You might be thinking what is the harm in drinking water, isn’t staying hydrated a healthy behavior? 

…But you order a basic metabolic panel and find the persons sodium is 125 mEq/L. 

Now the panic sets in, it’s time to worry and the patient continues to complain of feeling thirsty and is noted to be urinating frequently. 

There are a few possibilities for the persons behavior, but we need to consider psychogenic polydipsia or primary polydipsia. This was first described in the 1930s in patients with schizophrenia who drank water excessively resulting in low serum sodium levels. 

The cause is unknown, but these patients may have an acquired defect in the hypothalamic thirst regulation. Medications have also been associated with worsening of psychogenic polydipsia. It’s thought to be related to the anticholinergic effects of many of these medications. Examples include carbamazepine, chlorpromazine, oxcarbazepine, haloperidol, and valproate. 

Psychogenic polydipsia (PP) is common, and it’s usually associated with schizophrenia but can occur in other psychotic, mood, and anxiety disorders. Some users of MDMA also develop PP. 

PP is a primary problem where the patient is drinking too much water. This results in a dilution of the blood and thus a low sodium level (defined as < 135 mEq/L) and low serum osmolality. The urine will also be dilute < 100 mOsmol/kg with low urine sodium. 

Two other potential places where we can see polyuria are in cases of hyperglycemia from uncontrolled diabetes and nephrogenic diabetes insipidus. The key distinction in the first case is hyperglycemia. The water is drawn out by osmotic diuresis secondary to excess glucose in the urine. The key labs here are a fasting glucose and a urine analysis which should show hyperglycemia and glucose in the urine. In nephrogenic diabetes insipidus the brain secretes ADH just fine, but the kidney does not respond to it. The urine will be dilute, but the serum sodium level will be high not low separating it from psychogenic polydipsia.

Treatment includes fluid restriction to 1000-1500 mL/day, this can be difficult to enforce even on an inpatient unit. The person may need to be watched because sources like the bathroom sink or even toilet may be used to consume more water. This is usually enough of a treatment, but should the sodium remain low you can add sodium chloride tablets 1-3 grams daily. 

In severe cases where the sodium drops below 120 the person can have a seizure. In these cases, it’s best to handle the fluid replenishment on the medical floor with 3% saline. 

You must be careful not to correct the sodium too rapidly as it can result in the dreaded central pontine myelinolysis which can result in quadriparesis. That’s why we correct the sodium at a rate of no more than 10 mmol/L/24 h or 0.5 mEQ/L/h 

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Major Depressive Disorder (MDD) With Psychotic Features

This is a diagnosis that I often receive questions about. It can be confusing, how do we know if the person has schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features? 

They all have psychotic symptoms such as delusions and hallucinations.

In this video I’m going to explain how we navigate this diagnostic dilemma. 

For one to be diagnosed with MDD with psychotic features they must meet criteria for major depressive disorder based on the DSM-5TR. 

As a reminder, to meet criteria the person must have 5 out of 9 symptoms within a two-week period and at least one symptom must be either depressed mood or loss of interest. 

In medical school they teach you the mnemonic SIGECAPS, an interesting fact is this is written the way you would fill out a paper prescription for depression. SIG Energy Capsules which you would give to a person with major depression because of the low energy and loss of interest commonly seen in major depression. 

Anyway…

The other criteria include 

-Weight loss or weight gain 

-Insomnia or hypersomnia 

-Psychomotor agitation or retardation 

-Fatigue or loss of energy 

-Feelings of worthlessness or guilt 

-Poor concentration 

-Recurrent thoughts of death or suicidal ideation 

So, we have a person who meets criteria for MDD, they have 5 out of 9 symptoms for a two-week period. 

We should keep in mind it’s important that the person has also suffered some loss of function in their personal or professional life because of the symptoms. This is what makes it a disorder. 

Now, what if the person also has a loss of reality-based thinking in conjunction with the major depressive episode?

This will include things like delusions and hallucinations. The delusions can be persecutory in nature or paranoid, but other types may occur too. The persecutory delusions are ones where the person feels attacked or victimized by others. They may even believe people are coming into their home to harm them. This usually presents with the patient reporting things being moved in the home or things being out of place. A common paranoid delusion is one where the person believes they are being followed. This usually presents as a car or person the patient keeps seeing, and they cannot believe that it may just be a coincidence, or someone who travels the same route to work every day.

Delusions are fixed false beliefs, and although there may be rational explanations for the things going on around them, this is the patient’s reality, and you must be careful when challenging it. The belief is fixed, and That is why presenting evidence contrary to the belief is not effective.  

The important point here is the psychotic symptoms are only present during the major depressive episode. Treat the depression and the psychotic symptoms resolve. If the psychotic symptoms remain after the major depressive episode is successfully treated, you need to reevaluate the diagnosis.

This is what separates MDD with psychotic features from schizophrenia. 

In bipolar disorder with psychotic features, the psychosis often occurs in the manic phase of the illness and has a grandiose theme associated with it. The patient my for example believe they are a prominent religious figure, or the government is plotting against them. 

We often call the delusions in depressive episodes mood congruent, meaning they are consistent with how the person is feeling. It’s not a far stretch for a person who is severally depressed to feel like people want to harm them. 

Treatment

Treatment is well established and consists of an SSRI or other antidepressant medication in combination with a dopamine blocking medication. The other option is electroconvulsive therapy (ECT) when the person is severally depressed not eating, attending to ADLs, or at risk for suicide. 

Patients should remain on medication for at least 6 months after complete resolution of symptoms. This is very important as relapse has been proven to occur when medication is stopped prior to that time. People can taper off the dopamine blocking medication after 6 months as these tend to have worse side effect profiles. The SSRI should be continued for 1 year at which time you can attempt to taper off or reach a lowest effective dose if symptoms begin to reappear. An index phase of ECT should be completed if that is the treatment of choice which consists of 12 total sessions done either 2 or 3 times per week. 

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Malingering In Psychiatry

  • Let’s first define malingering, this is the production of false or grossly exaggerated physical or psychological symptoms motivated by external incentives. 
  • Not all lying involves secondary gain, but ALL malingering does involve secondary gain 
  • Common secondary gains include avoiding military service, avoiding work, financial incentives, avoiding legal actions, and obtaining controlled substances 
  • Feigning mental illness is not the same as malingering because the reason behind the false production of symptoms is not assumed with feigning symptoms. 
  • Factitious disorder is the voluntary production of symptoms, but this is with the goal of assuming the sick role or role of a patient, it’s not done for secondary gain. 

Consider malingering when….

-Rare symptoms are present 

-Improbable symptoms are being reported

-Rare combination of symptoms are present

-Reported Vs observed symptoms are not congruent

Malingered Depression:

-25-30% of patients who claimed major depression in civil litigation were probably malingering

-Pay careful attention to facial expressions 

-Pay careful attention to motor function, psychomotor retardation is an important observable sign

-If appetite changes are reported look for actual objective weight change 

-symptoms opposite of depression 

-blaming others for everything is not the way guilt typically presents in depression, this is externalizing and not taking personal responsibnility

Malingered Psychosis: 

-Often in true psychosis people can describe the voice/s, is it loud, soft, male, female, you have some experience of what you heard. When you ask a malingering patient about a voice, they should have some ability to describe what they are hearing, if not consider malingering.

-If you are suspicious, begin with open ended questions, ask them to describe things in their own words. 

-Genuine AH are in words or sentences, drug Hallucinations usually occur as unformed noises.

-The location of the voice inside the head or outside is no longer a good predictor of malingering 

-Many times the content of voices are derogatory in nature

-Other signs of malingered psychosis include Vague or inaudible auditory hallucinations, AH not associated with delusions (86% of AH have an associated delusion), no strategies to diminish voices 76% of patients have some coping strategy to diminish the voices. They claim that all instructions are obeyed, the hallucinations are visual alone, seeing little people or giant people for example.

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Schizoaffective Disorder: A Confusing Diagnosis

Introduction: 

  • Schizoaffective disorder has features of both schizophrenia and mood disorders (bipolar and depression). 
  • Two sub types: depressed type and bipolar type 
  • The diagnosis can get complicated because primary mood disorders can have psychotic features (MMD with psychotic features or bipolar disorder with psychotic features), patients with schizophrenia can have mood symptom most commonly depression. 

Epidemiology:

  • The lifetime prevalence is less than 1%, the most recent data indicates 0.3% but I would say there is a range between 0.5-0.8%
  • More women have the depressed type greater than 2:1 ratio 
  • Equal number of men and women have the bipolar type 
  • The cause of schizoaffective disorder is unknown. It may be a type of schizophrenia, a type of mood disorder, but most likely it’s a spectrum that combines all these things.
  • Schizoaffective disorder has a better prognosis than schizophrenia but a worse prognosis than primary mood disorders. 
  • Patients are said to have a nondeteriorating course and respond better to lithium than patients with schizophrenia. 

Diagnosis:

  • Schizoaffective disorder combines the features of both schizophrenia and affective mood disorders. 
  • If the mood is primarily manic, it’s called schizoaffective disorder bipolar type 
  • If the mood is primarily depressed it’s called depressed type 
  • The mood component should be present for the majority > 50% of the total illness 
  • You must have a two-week period where psychotic symptoms and are present in the absence of mood symptoms

Treatment:

  • Treatment will depend on the predominant symptoms. If the patient has more mania than a mood stabilizer will be used (e.g., lithium) 
  • For psychotic symptoms, dopamine blocking medications will be used (e.g., risperidone) 
  • For depressive symptoms serotonin reuptake inhibitors will be used (e.g., sertraline)
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Diagnosis Depression: Major Depressive Disorder (MDD) With Psychotic features

In the last post we covered MDD and we introduced the specifiers. In this post I will talk about MDD with psychotic features. 

You may have guessed already, but what separates this disorder from MDD is the presence of delusions, and hallucinations along with symptoms of major depression. Fairly simple, right?

First, we need to define psychotic symptoms. 

In general, we can think about the following symptoms: 

  1. Delusions: which can be defined as fixed false beliefs. Something that the person believes despite evidence to the contrary. 
  2. Hallucinations: A hallucination is a sensory perception in the absence of external stimuli. There are several types including auditory (most common, consists of hearing a voice or several voices), visual, olfactory (smell), tactile (touch), and gustatory (taste). 
  3. Disorganized speech or behavior: This is an indication of the persons thought process. If the person is not thinking in a clear logical manner their though process may be difficult or impossible to follow for an outside observer.  

These psychotic symptoms can be congruent with the depressed mood (content is consistent with depressive thoughts) or mood incongruent (content is not consistent with typical depressive thoughts). Mood congruent psychotic symptoms will consist of depressive themes such as guilt, death, poor self-worth, and punishment. Mood incongruent symptoms include things such as delusions of control, thought broadcasting, or thought insertion. Both mood congruent and incongruent themes can occur in the same episode.  

Another key point is the psychotic symptoms only occur during a depressive episode. They are not present when the patient is not depressed. Once psychotic symptoms appear with an episode of depression, they tend to be present on subsequent episodes. 

In the next post we will cover atypical features of depression. Please like, comment, and share the content. Feel free to offer suggestions for future posts. 

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