TCPR: So I’m interviewing a patient in the clinic; I have only 45 minutes to do a thorough psychiatric evaluation. I’m rushed; I don’t have enough time to really learn all I want to know. It would be great if there were a list of specific red flags to say, “OK, this person has a medical disorder that’s either complicating or generating a lot of the ‘psychiatric’ symptoms I am seeing.”

Dr. Schildkrout: Well, there are some specific red flags that indicate you are definitively dealing with a medical disorder. I’m thinking of signs like slurred speech, clouding of consciousness, overt confusion, or physical abnormalities that you can see from across the room, such as jaundice or an abnormal gait. But many clinic patients won’t have these signs. Then you’re mainly looking for clues that there is something atypical about this presentation or this patient. Your job is to think beyond the DSM and to keep the possibility of a medical disorder in mind. Many patients are not getting regular medical care, so although you are not a PCP, you may be the one doctor they actually see. As a physician, it makes sense to do a mental status exam and a medical review of systems, even if you do them quickly. These may reveal something that is new. 

TCPR: I agree. Let’s start with depression, which is something we commonly see in outpatient practice. What are your thoughts about potential medical issues masquerading as depression?

Dr. Schildkrout: It’s always important to distinguish depression from apathy. Depression is a disturbance of mood, whereas apathy is about motivation. Apathy is impairment in the process of getting yourself going, of initiating, and then following through. The two are related in that when you’re depressed, you don’t have a zest for life and don’t feel as invested in doing things. So it’s easy to confuse the two. People who have apathy may talk less, may not engage in activities, and they may not even initiate conversation. And this may be interpreted as depression. But if you ask somebody who’s simply apathetic what they’re feeling, they will tell you, “No, I’m not depressed.” Apathy is more associated with brain phenomena, so this is something to definitely consider in your older patients (Epstein J and Silbersweig D, J Neuropsychiatry Clin Neurosciences 2015;27(1):7–18. doi:10.1176/appi.neuropsych.13120370). 

TCPR: So apathy is something we might attribute to a medical condition?

Dr. Schildkrout: Yes, apathy is related to neural circuitry of the frontal lobes. A person who is apathetic could have an underlying medical problem such as a frontal lobe tumor, frontal dementia, chronic subdural hematoma, or normal pressure hydrocephalus. Apathy could also be related to traumatic brain injury (TBI).

TCPR: So a patient may volunteer something like, “I had a concussion” or “I was in a bad auto accident,” and you can ask screening questions like, “Have you had a head injury?” or “Have you ever been knocked unconscious?” Then you’re faced with, “OK so it’s happened; now what?” Is it the TBI that has worsened the psychiatric condition, or is it the psychiatric condition that is causing the cognitive problem?

Dr. Schildkrout: Right, the TBI could be completely irrelevant. Or, as we know, there is the potential for secondary gain after a head injury. But there’s also the interaction of a head injury with any antecedent psychiatric disorder, making a psychiatric condition worse. Or, the TBI could be significant in itself. Sorting this out is what makes our job so complicated. First, try to figure out how serious the head injury was. Ask how long the person was unconscious and how long was the period of amnesia afterwards. What’s the last thing the patient remembers from before the injury, and when did their memory resume afterwards? Second, determine what the patient was like before the head injury compared to what the patient is like now. Has there been a change in personality? If you haven’t known the patient over time, then you don’t know whether the person you’re seeing is now substantially different than before the injury. To get that information, you have to talk to family members or friends and also try to get surrogate measures like work history, school history, grades, social involvement, and so on. 

TCPR: That’s very important information. Getting back to depression, are there any other features that increase your index of suspicion that there’s a medical problem?

Dr. Schildkrout: It’s important to note whether the age of onset is typical, or whether the first episode came on later in life. Having no family history of mental illness is also a red flag. Also, pay attention if there are a lot of physical symptoms that accompany the depression, such as significant weight change, arthritis, headaches, cough, gastrointestinal symptoms, gait instability, and so on. 

TCPR: OK, let’s say we have a late-onset depression patient without a family history and it’s a first episode. We have ascertained that our patient is experiencing depression and not apathy. What kinds of questions should that bring up?

Dr. Schildkrout: Some of the things I’d be thinking of include sleep disorders which are very common; underlying malignancies like pancreatic and lung cancer; endocrine disorders such as hypothyroidism; multiple sclerosis; and early Parkinson’s disease. Many medical diseases can present with depression, so you have to cast a wide net looking for clues. I would ask my patient, “How has your general health been? Do you have any physical complaints? Have you had constipation? How is your sleep? How do you feel when you wake up in the morning?” I realize that depression alone may cause problems in many of these areas, so you have to inquire carefully about the severity of the symptoms.

TCPR: Let’s say something suddenly something jumps out at you and now you’re thinking maybe Parkinson’s. Where are your questions headed to try and ascertain that potential condition?

Dr. Schildkrout: If I have a depressed patient and I’m thinking, “Hmm, maybe this is the beginning of Parkinson’s,” then physically I’ll watch this person very carefully. Is there any paucity of movement? A tremor? How is the person’s gait? Is their voice soft? I’m also going to ask more specifically about changes in handwriting, which can get smaller with Parkinson’s disease, and about constipation, which is also common. I’d ask questions about sleep such as, “Have you ever fallen out of bed?” and “Does your partner complain that you move a lot in your sleep or act out your dreams?” REM sleep behavior disorder is often a prodrome of Parkinson’s and can begin up to 10 years in advance. Patients don’t necessarily talk about these nighttime behaviors because they may feel embarrassed. REM sleep behavior disorder can be an important harbinger of a later onset of Parkinsonian spectrum disorder—including some disorders that are rare, like multiple systems atrophy and so on (Kalia LV and Lang AE, The Lancet 2015;386(9996):896–912. doi:10.1016/S0140–6736(14)61393–3).

TCPR: You also mentioned endocrine and thyroid disorders as possible causes of depression. What kinds of questions would you ask to identify those symptoms?

Dr. Schildkrout: For the thyroid disorders, I’d ask about whether the person has noticed any change in temperature sense, being especially hot or cold. Do they fight with a partner about the bedcovers or how to set the thermostat? There is often a drying and coarsening of skin or hair with hypothyroidism and a thinning with hyperthyroidism. I’d ask about hair loss and nail cracking, as well as recent weight gain or loss, fatigue, and constipation. Hypothyroidism classically presents with depression, but in older individuals especially, hyperthyroidism also can present as depression. Anxiety, irritability, and insomnia can accompany thyroid disorders, so I would be asking more specific questions about those areas as well.

TCPR: You brought up a common symptom: anxiety. We are almost always going to have patients saying that they’re anxious—whether it’s part of their depression or a distinct anxiety disorder. What kind of medical problems can produce symptoms of anxiety?

Dr. Schildkrout: Well, if we focus on “anxiety attacks,” pheochromocytoma is a rare condition that can mimic panic attacks. More commonly, though, episodes of anxiety can be associated with partial seizure disorders. During a seizure, there can be an experience of anxiety and fear that comes out of the blue. This is another instance in which it is crucial to listen carefully to the words the patient is saying. Does the person experience anxiety or fear? Fear is more characteristic of a seizure, but people may report a lot of anxiety before or after an episode. Patients who are having multiple seizures may have a lot of anxiety in between the seizure episodes.

TCPR: So if we have some suspicion of seizure, do we automatically refer a patient to a neurologist? We don’t want to over-refer people for tests such as EEGs because of cost and potential false-positive results, correct?

Dr. Schildkrout: Yes, it’s tricky. It can also be challenging to find neurologists who know a lot of about seizures outside an academic center area. You have to determine your level of certainty about whether your patient really is having seizures. And that is partly based on whether the patient’s symptoms are classical for focal seizures: 1) episodes that are stereotypical for the individual, although a patient may have more than one type of episode; 2) episodes that come on “out of the blue” and that have typical features. 

TCPR: What are some of these typical features?

Dr. Schildkrout: The list of possible seizure-related symptoms is huge, but the typical ones are: fear or a sense of dread or impending doom; sensations in the chest or abdomen; frequent déjà vu experiences; alterations in one’s sense of reality, including dissociative episodes; hallucinations of smell, taste, or sound; and possible visual or kinesthetic illusions or hallucinations. And these episodes don’t last very long, usually minutes and are often followed by fatigue (Schomer DL et al, Principles of Behavioral and Cognitive Neurology 2nd ed. Oxford, England: Oxford University Press; 2000:373–405). This presentation is absolutely classical, and anyone experiencing this constellation of symptoms surely needs a workup. If we are talking about less typical symptoms then you have to make a judgment call. One final thing—look at the symptoms in the context of the person’s whole character.

TCPR: Can you be more specific?

Dr. Schildkrout: Yes. Here’s an example. I know of a patient who was in psychotherapy for a psychological condition and who reported brief episodes of hallucinations of the smell of rotten eggs. She suffered from extreme anxiety at times and experienced emotions very intensely, but not in the context of a borderline personality disorder, narcissistic disorder, or bipolar diagnosis. The patient was very mature and related well interpersonally. Her symptoms had been going on for years. Keep in mind that intensification of emotions has been hypothesized to be related to repeated firing of limbic circuitry, as occurs with tempo-limbic seizures. Although the patient responded to lamotrigine, she never had a documented abnormal EEG. She eventually did see an epileptologist. Her screening EEG was negative, and the epileptologist didn’t want to do a more extended evaluation. I believe that the patient’s emotional presentation was throwing the specialist off track; a psychiatric diagnosis seemed most likely to the specialist. The psychiatrist ended up contacting the epileptologist afterwards to advocate that this patient’s case needed to be further pursued. The situation had been very seriously thought through; there were good reasons to believe that this woman had a long-standing seizure disorder, that there was a deep focus, and that that was the reason for the absence of findings on the screening EEG. 

TCPR: Was the conversation successful? How was the psychiatrist able to get the doctor to take it seriously?

Dr. Schildkrout: Yes, it was a successful conversation. I think part of the reason was that the psychiatrist really knew the history of the patient’s response to lamotrigine: the olfactory hallucinations, and the fact that although she experienced very intense emotions, the patient was an emotionally healthy person. This gets us back to the point—seeing symptoms in the context of the whole person.

TCPR: You bring up an important point that I think we as psychiatrists wrestle with—am I providing a good enough level of care if I’m not in contact with my patient’s primary care physician or other doctors? In a typical day we may have a patient who comes in with a fairly complicated psychiatric presentation who has a primary care doctor, is being treated for diabetes or a cardiac condition, and has a few medications on board. I think it is probably the rare psychiatrist who has time to pick up the phone and call that patient’s primary care doctor.

Dr. Schildkrout: The primary care doctors often don’t have a lot of time either. So it’s a challenge on both ends. Initially, what I do is work through the patient; I emphasize that the issues we are talking about need to be discussed with a primary care doctor or specialist. But there are times when I feel that a certain concern of mine isn’t something that the patient can convey. Sometimes I need to have a personal conversation with the PCP in order to “be on the same page,” or to work out some kind of conflict or misunderstanding. This is when I pick up the phone. 

TCPR: Is there a particular medical condition in which you often find yourself consulting with a patient’s PCP?

Dr. Schildkrout: Yes, dementia, especially if the person is lacking in insight.

TCPR: We know that some of the early symptoms of dementia are changes in personality, changes in the way people respond to others. What are some other symptoms we might miss or might not necessarily associate with this illness that we should be looking for?

Dr. Schildkrout: You just mentioned a couple: a loss of empathy, disinhibition, and apathy, failing executive functions and social withdrawal. Especially in older patients, these can present as depression. Keep in mind that many patients are knowledgeable about Alzheimer’s disease and may willingly report memory complaints. But I think they’re not as tuned into the kinds of behavioral changes that can occur with frontal dementia, such as poor judgment, lack of insight, or obsessional behavior, particularly related to eating, hoarding, etc. (Block NR et al, Am J Geriatr Psychiatry 2015 (15)00188–8.doi:10.1016/j.jagp.2015.04.007 [Epub ahead of print]). Generally, the OCD behavior associated with dementia is somewhat atypical in that the person doesn’t necessarily feel distressed by their symptoms. Dementia patients may also have delusions and hallucinations. With Lewy body dementia, which is actually very common, visual hallucinations are an early symptom. Psychiatrists need to be especially aware of Lewy body disease because if patients with this disease are prescribed an antipsychotic, it can make the dementia precipitously worse. If you have a suspicion of this disease, you should check the patient’s history for atypical reactions to medications like Haldol. Psychotropic medications make these patients much worse, so that kind of history can lend support for a Lewy body dementia diagnosis.

TCPR: That’s important information to know. Any other presentations we should watch out for?

Dr. Schildkrout: What psychiatrists often see is someone with a change of circumstances who is unable to adapt. A patient may come in feeling depressed or overwhelmed because of a recent move or the death of a partner, but in fact this could be the presentation of an early dementia in which the person has lost adaptive flexibility. Many people with early dementias are able to keep up established routines that don’t involve new learning. But these same individuals, faced with something like a move from their familiar neighborhood, will find it problematic to learn the new things that are involved in adapting to the change of circumstances. So that’s another way that dementias may present to psychiatrists. Also, keep in mind that it isn’t just the elderly who can develop dementia; frontal dementias can present in mid-life, and there are people with strong genetic family histories of Alzheimer’s who can present as early as in their 30s.

TCPR: That is very valuable insight. Thank you, Dr. Schildkrout.