The six-step differential diagnosis tool is an approach to properly diagnosing mental health disorders.

Differential diagnosis ensures that doctors consider all possibilities before they make a diagnosis for a patient’s illness. It involves making a list of all possible explanations for a patient’s symptoms and eliminating each one until only the correct diagnosis is left. Often, doctors use differential diagnoses for mental disorders like depression. 

It is not hard to imagine the consequences of an incorrect or missed diagnosis. When it happens, the actual problem doesn’t get treated or addressed. People may be subjected to potentially harmful treatments and testing for an illness that they don’t even have. 

Differential diagnosis is a difficult process, and it is a major focus of doctors’ medical training. The process is very operator-dependent, so some doctors are better at it than others. The ones who are not as efficient at it are likely to be error-prone when diagnosing and treating their patients. 

What Is a Differential Diagnosis?

Health care professionals typically conduct a differential diagnosis, meaning they make a list of all the possible explanations for a person’s symptoms and eliminate them one by one.

The differential diagnosis then guides the rest of the assessment of the patient. When doctors ask patients a long list of questions, they are narrowing down the list of possible explanations. After asking these questions, doctors then do a physical examination and order lab tests or imaging (such as x-rays or ultrasound tests). These help them narrow down the differential diagnosis, arrive at a diagnosis, confirm the diagnosis and come up with a treatment plan.

What is a differential diagnosis for mental health? Most mental health disorders cannot be diagnosed by any lab tests or imaging tests. However, the tests are still done to help eliminate physical ailments that may mimic mental health disorders. For example, blood tests will help make sure that what appears to be depression is not really hypothyroidism, vitamin B12 deficiency or iron-deficiency anemia.

The Process of Differential Diagnosis

The six-step differential diagnosis process described below is taken from the DSM-5 Handbook of Differential Diagnosis by Dr. Michael First. In his book, Dr. First shows how to form a differential diagnosis for a mental health disorder by using a six-step framework. Dr. First bases his six-step process on the DSM-5 differential diagnosis.

DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) is the internationally accepted guidebook for diagnosing mental health disorders. It contains detailed lists of diagnostic criteria, symptoms, and stipulations for every accepted mental health disorder. 

Step 1: Rule Out Malingering and Factitious Disorder

To work through the differential diagnosis and find the correct illness, a doctor requires cooperation and honesty from the patient. It can be very challenging to figure out if the patient is exaggerating or even making up the symptoms. When this deception occurs, it is usually due to either malingering or factitious disorder.

Malingering is when individuals purposely try to deceive the doctor. Pure malingering means the patient is making up the symptoms, and partial malingering means they are simply exaggerating. 

Malingering is motivated by trying to gain something from feigning illness, such as:

  • Obtaining an insurance settlement
  • Getting disability benefits
  • Avoiding work
  • Avoiding punishment or incarceration
  • Getting out of jury duty
  • Avoiding military service or deployment
  • Obtaining drugs from the doctor

Some malingerers may research the disease that they are faking and even try to falsify lab tests (faking kidney stones by placing blood in their urine, for example). Therefore, doctors must be very alert to pick up on the deception.

Factitious disorder is a mental health disorder, unlike malingering. People with factitious disorder do purposely makeup symptoms and try to deceive their doctors. The difference, however, is that these people are not doing it for their own gain. Rather, they have a psychological need to play the sick role and receive attention. They will even go through dangerous surgeries as part of their deception. Factitious disorder by proxy is when the individual fakes an illness in someone else, such as a child.

The faked illness must be considered and ruled out to the best of the doctor’s ability before making a diagnosis.

Step 2: Rule Out Substance Etiology

Every diagnosis in the DSM-5 states that the illness must not be “attributable to the physiological effects of a substance.” That is because substance use or withdrawal from substance use can mimic many mental health disorders.

Mental health disorders and substance use disorders share many commonalities:

  • Substance use disorders are mental health disorders
  • They frequently co-occur (this is known as comorbidity)
  • They share many of the same genetic causes
  • They share many symptoms in common
  • They share many of the same risk factors
  • They share many of the same brain chemical (neurotransmitter) imbalances
  • They share many of the same dysfunctional brain pathways
  • They can and often do cause each other

Because of these similarities, it is important to rule out substance use and substance-induced symptoms before diagnosing a mental health disorder. This can be difficult because people who misuse substances are often reluctant to admit it even to their doctor, fearing arrest or other consequences. Being secretive and lying about substance use is one of the core symptoms of addiction.

Fortunately, laboratory testing helps with this. Urine drug testing can detect most substances for days after the drug was last used:

Lab tests are getting better all the time, so these testing times are always improving. However, some substances that can cause mental health symptoms are not detected by usual lab tests, such as LSD, mushrooms, and MDMA.

Step 3: Rule Out a Disorder Due to a General Medical Condition

There are many general medical conditions that can cause mental health symptoms. Nearly every diagnosis in the DSM-5 states that causative general medical conditions must be ruled out prior to diagnosing a mental health disorder.

Psychiatrists are not experts in assessing patients for medical conditions. They often rely on other doctors to “medically clear” patients before they will assess for mental health disorders. The list of illnesses that can cause mental health symptoms is long, so it can be a very challenging process to rule out a general medical condition.

To make matters worse, medications used to treat general medical conditions can cause mental health symptoms as well, including:

  • Some antibiotics
  • Stimulants
  • Opioids
  • Cannabis
  • Parkinson’s disease medications
  • Some antibiotics
  • Corticosteroids
  • Anti-seizure medications
  • Some heart and blood pressure medications
  • Cough medicines

Doctors must determine if a medical condition or medication is causing mental health symptoms or unmasking a pre-existing mental health disorder. Generally, if the medical condition came before the mental health symptoms, the medical condition is usually the culprit. 

Step 4: Determine the Specific Primary Disorder

At this point, the doctor must determine which mental health disorder is responsible for the patient’s symptoms. This can be much more difficult than it sounds since many mental health disorders overlap considerably.

One factor that contributes to most mental health symptoms is brain chemistry disruption. In particular, symptoms can be caused by an imbalance of neurotransmitters, which are chemicals the brain cells use to communicate with each other. Because many mental health disorders occur from neurotransmitter imbalances, there is a great deal of overlap in symptoms. This makes finding the right diagnosis challenging.

The DSM-5 provides 66 diagnostic tables and 29 symptom flow-charts that are referred to as “decision trees.” These help doctors differentiate between the various symptoms and disorders and come to a conclusive diagnosis. For more complicated disorders, diagnosis may take some time to fine-tune.

Step 5: Differentiate Adjustment Disorders From the Residual Other or Unspecified Disorders

In this step, Dr. First suggests ways to deal with symptoms that don’t fit into any particular diagnostic category. This involves deciding if the undiagnosed symptoms constitute an adjustment disorder, which is an exaggerated and persistent psychological response to some kind of life event. Alternatively, doctors must decide whether symptoms should be categorized as “unspecified” if they do not fit into other diagnoses.

Step 6: Establish Boundary With No Mental Disorder

This is the step where doctors do a “gut check” to see if the mental health symptoms are significant enough to amount to a mental health disorder. According to DSM-5, the symptoms must be severe enough to “cause the individual clinically significant distress or impairment in social, occupational, or other important areas of functioning.” 

Generally, if the symptoms are bothersome enough to cause the individual to seek help, they are severe enough to be part of a mental health disorder. However, there are some exceptions. For example, someone grieving the recent loss of a parent may be suffering difficulty with sleeping and functioning. They may see a doctor to get a mild sedative and some time off work, but that is just normal bereavement and not necessarily a mental health disorder. Doctors must be able to make a judgment call.

Machine Differential Diagnosis

Machine differential diagnosis refers to using technology to assist in making a differential diagnosis. Some types of medical software help with differential diagnosis and even provide questions to ask. However, these tools cannot replace the expertise of a trained and experienced doctor. In its current state, no doctor would rely on such technology for anything more than a simple memory aid.

In addition to these tools, there are medical information databases that doctors can access. The databases help them find detailed information about various diagnoses on a case-by-case basis.

Machine differential diagnosis will likely use artificial intelligence and data networks in the future. However, due to the potential harm these systems could be capable of, it will be some time before they are reliable enough to enter clinical use.

In the meantime, differential diagnosis relies on human training and ingenuity to properly diagnose mental health disorders. The degree of expertise and experience of the doctor remains crucial.

The Recovery Village is staffed by professionals who have expertise in substance use disorders and co-occurring mental health disorders. If you are affected by addiction and a co-occurring mental health disorder, contact us today to learn more about evidence-based treatment options.

a man wearing a blue and white striped shirt.
Editor – Jonathan Strum
Jonathan Strum graduated from the University of Nebraska Omaha with a Bachelor's in Communication in 2017 and has been writing professionally ever since. Read more
a man in a suit and tie smiling at the camera.
Medically Reviewed By – Dr. Andrew Proulx, MD
Andrew Proulx holds a Bachelor of Science in Chemistry, an MD from Queen's University, and has completed post-graduate studies in medicine. He practiced as a primary care physician from 2001 to 2016 in general practice and in the ER. Read more

Bass, Christopher; Halligan, Peter. “Factitious disorder and malingering: Challenges for clinical assessment and management.” The Lancet, March 5, 2014. Accessed June 7, 2019.

Davis, Rachel. “DSM-5 handbook of differential diagnosis.” The American Journal of Psychiatry, May 1, 2014. Accessed June 7, 2019.

First, M. “DSM-5 Handbook of Differential Diagnosis.” American Psychiatric Publishing, 2014.

Hadland, Scott; Levy, Sharon. “Objective testing: Urine and other drug tests.” Child and Adolescent Psychiatric Clinics of North America, July 2016. Accessed June 7, 2019.

Maung, Hane. “Diagnosis and causal explanation in psychiatry.” Studies in History and Philosophy of Biological and Biomedical Sciences, December 2016. Accessed June 7, 2019.

McKee, Jerry; Brahm, Nancy. “Medical mimics: Differential diagnostic […]sychiatric symptoms.” Mental Health Clinician, November 3, 2016. Accessed June 7, 2019.

National Institute on Drug Abuse. “Comorbidity: Addiction and other mental illnesses.” Research Report Series, September 2010. Accessed June 7, 2019.

DSM Library. “Other Mental Disorders and Additional Codes.” September 25, 2014. Accessed June 16, 2019.

Medical Disclaimer

The Recovery Village aims to improve the quality of life for people struggling with substance use or mental health disorder with fact-based content about the nature of behavioral health conditions, treatment options and their related outcomes. We publish material that is researched, cited, edited and reviewed by licensed medical professionals. The information we provide is not intended to be a substitute for professional medical advice, diagnosis or treatment. It should not be used in place of the advice of your physician or other qualified healthcare providers.