Medication for SMI

Learn about medications to treat SMI conditions, including key vocabulary and an approach for supporting someone unable to manage medication independently. 

What do I need to know about medication management for SMI? 

Understanding what psychiatric medications are available and how they might be dosed and combined can feel daunting. Significant side effects are common, and not always well managed. Most complicated of all is that people with severe mental illness (SMI) often cannot understand that they have an illness because of a symptom that blocks insight (anosognosia); taking medicine for an illness they genuinely believe they don’t have understandably makes no logical sense to them. 

The situation is further complicated by a severe provider shortage and significant federal cuts to already under-resourced community mental health programs and public insurance. As specialty programs close, more metropolitan areas join rural areas in reliance on primary care to address mental health needs. Many primary-care doctors lack specialized training to treat SMI.  

By SMI, TAC means schizophrenia spectrum, bipolar, and depressive disorders that are significantly life-altering and usually come with psychosis. While many primary care physicians have become accustomed to screening for depression or anxiety, they are less likely to have experience with SMI. Medication management for SMI requires close monitoring to establish and maintain stability.  

Who can prescribe psychiatric medication depends on provider availability as well as state licensure laws and policies. Some locations require a psychiatrist to oversee prescriptions for complex mental health conditions. That can be limiting, as private psychiatrists often don’t accept insurance and may refuse to treat patients with SMI, a practice known as “cherry picking.” In his seminal book, “Insane Consequences,” the late D.J. Jaffe details how privatization incentivized treatment for mild or moderate conditions over conditions that are persistent and severe. In light of these barriers, some state laws have expanded to allow qualified nurse practitioners, physician assistants, and psychologists to independently prescribe psychiatric medication.  

More than a fifth of people with mental health disorders have Medicaid insurance, creating a number of barriers related to medication management. In June 2025, research indicated that states spend more overall when they attempt to cut costs by strictly limiting access to psychiatric medications with strategies such as “prior authorization” and “step therapy,” which requires a generic medication to “fail” before a name-brand medication is reimbursable. Advocacy is needed to support open access to effective psychiatric medications, regardless of a person’s insurance plan.

Medication is one tool for treatment 

Medication alone is rarely adequate to enable enduring long-term recovery for someone with SMI, though it is often key to stabilization. Cognitive behavioral therapy for psychosis (CBTp), cognitive enhancement therapy (CET), psychoeducation, supportive housing, and vocational assistance can provide critical supports. Various evidence-based treatments are described in TAC’s article about the continuum of care.  

Psychosocial interventions are included in long-standing best-practice guidelines from the American Psychiatric Association (APA), which recommends that a care plan also include person-centered skill-building in self-management and social skills. Additional guidelines about the most evidence-based treatments for schizophrenia were announced April 16, 2025, on Psychiatrist.com: INTEGRATE, which stands for International Guidelines for Algorithmic Treatment, is a set of guidelines developed by a global team of experts. The guidance prioritizes early interventions and patient-centered approaches and makes specific medication recommendations that are incorporated into this resource.   

Although whole-person care is key to long-term outcomes, psychiatric medication may be the first and most necessary tool to enable a person with SMI to stabilize enough for a broader treatment plan to work. For example, expecting a person in active psychosis to work on a vocational goal or person-centered skill-building is probably unrealistic. Understanding how to advocate for high-quality medication management is an important aspect of personal advocacy. If medication management is poor, filing a complaint may be an option. 

Maintain a medication log 

A careful record of medications with their dosages, effects, and side effects can be critically important for collaborative decision-making with any provider.  TAC provides a downloadable form to help you build and maintain a medication log. Here is the form below:

The log should list all current and past medications. If a medication has been stopped, make a note about why. If there was an adverse reaction, documentation of that adverse event may prevent a future provider from making a mistake.  

A medication log should list the names of all medications and whether a brand name is necessary or if a generic form is used to the same benefit. The log should include dosages, date prescribed, the name of the prescriber, and the prescriber’s contact information. Additionally, the log should include notes about the medication’s effectiveness and any side effects. If medications are used in combination to ameliorate certain side effects, note the necessity for the combination of medications. This might include non-prescription supplements, if applicable.  

If a person turns up in a hospital, jail, or elsewhere and needs to request medication to maintain treatment, this information will be valuable in the moment. All care partners should keep a copy of the medication log, which should be kept as up-to-date as possible.  

Plan to share this information via fax whenever possible, as providers have added layers of accountability for information received through fax. Always include a cover letter highlighting the most important information, such as allergies or adverse reactions or what is likely to occur if a medication is withheld. Always include contact information for yourself and others with relevant mental health history.  

A family member or friend is not bound by HIPAA and can share all of this information without explicit permissions. TAC’s article about HIPAA has additional information, including what to do if you are worried that sharing information might jeopardize an important relationship. 

Here are two additional ways to track medication information and history: 

• • Make medication part of an up-to-date mental health history. TAC provides a fillable form: Mental Health History: Organize what providers need. 

• • Medication information is an important part of a psychiatric advance directive (PAD): TAC’s article can help you research this option for your state: Psychiatric Advance Directive (PAD): Crisis planning. 

A need for innovation 

Very few people with SMI receive comprehensive, evidence-based treatments that enable long-term recovery, and about half receive no treatment at all. In rural areas of the country, the numbers are worse. For those who access a prescriber and adhere to treatment, options are often limited to medications discovered decades ago. Those medications can leave some symptoms unaddressed and may cause debilitating side effects, including weight gain, diabetes, heart disease, sleep issues, and movement disorders. In many cases the older medications continue to offer the best prognosis, but side effects should still be actively managed since they can be a significant reason why people become nonadherent to treatment. 

Recent innovations show promise for next generation medicines that work differently. Among them are muscarinic receptor agonists, a class of medicines that alleviate a broader range of symptoms while avoiding many of the side effects associated with older antipsychotics.

The first of these medications, KarXT (Cobenfy) is also being studied for treating patients with Alzheimer’s-related psychosis. 

Although the development of new medications to treat SMI has been slow for generations and is much needed, innovation could be further slowed by reductions in research funding and changes to public insurance reimbursements being discussed at the federal level. A free, downloadable report with more detail is provided by the Schizophrenia & Psychosis Action Alliance: “Schizophrenia Medicines in Jeopardy.”  

Symptom-specific strategies 

Global guidance, INTEGRATE, makes these treatment recommendations based on specific symptoms commonly associated with schizophrenia spectrum disorders: 

• • Positive Symptoms (e.g., hallucinations, delusions): If first-line treatment fails after four weeks at a therapeutic dose, a different antipsychotic should be tried. If that treatment also fails, clozapine should be tried. Clinicians also should explore augmenting clozapine with: amisulpride (anti-nausea drug), aripiprazole (Abilify, an antipsychotic), or electroconvulsive therapy (ECT). 

• • Negative Symptoms (e.g., apathy, social withdrawal). After secondary causes of these symptoms are ruled out (depression, substance use, medication side effects), interventions might include reducing an antipsychotic dosage, switching to the antipsychotics cariprazine (Vraylar) or aripiprazole (Abilify), or adding low-dose amisulpride (anti-nausea drug). Psychosocial support remains vital. 

• • Depressive Symptoms. Antidepressants and psychological therapies should be tailored to meet individualized needs.  

• • Cognitive Symptoms. If a person experiences cognitive impairment, the blend of medications should be reviewed to determine if they are having a negative impact due to anticholinergic burden, caused by medications that reduce the neurotransmitter acetylcholine, which plays a role in thinking and can affect motivation and attention. Lowering dosages of antipsychotics and cognitive remediation therapies, such as cognitive enhancement therapy (CET), may help. 

Medications 

Please note that not all possible medication options are listed. 

Anti-anxiety medications: Often prescribed for insomnia or agitation, these might also address mania. Options: lorazepam (Ativan) and clonazepam (Klonopin). Please note that these medications may be habit-forming and therefore may not be a good option for some people. 

Anti-seizure medications: These might be used to stabilize moods. Options: valproic acid (divalproex/Depakote, approved for treating mania in 1995), lamotrigine (Lamictal, approved for maintenance of mood and/or depressive symptoms). 

Antidepressants: These may be prescribed to treat symptoms of depression in SMI conditions that include a mood disorder (such as bipolar and schizoaffective disorder), but may increase the risk of mania, hypomania, or rapid-cycling symptoms. When treating SMI, antidepressants are typically prescribed only in combination with mood stabilizers.  

• • Options: bupropion (Wellbutrin); or selective serotonin reuptake inhibitors such as fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft). 

• • Other choices if those do not work or cause unpleasant side effects: mirtazapine (Remeron), monoamine oxidase inhibitors such as phenelzine (Nardil) and tranylcypromine (Parnate); nefazodone (Serzone); tricyclic antidepressants such as amitriptyline (Elavil), desipramine (Norpramin, Pertofrane), imipramine (Tofranil), nortriptyline (Pamelor); and venlafaxine (Effexor). 

Antipsychotics: Used to treat symptoms of psychosis, which may be present in schizophrenia spectrum disorders as well as severe forms of bipolar and major depressive disorders. First-generation antipsychotics are “typical,” and second-generation antipsychotics are “atypical.” Some have long-acting injectable (LAI) versions. APA best-practice guidelines and global guidelines, INTEGRATE, recommend LAIs for people who need help with treatment adherence and clozapine for treatment-resistant illness.  

Perhaps surprisingly, some doctors may recommend stopping an antipsychotic after symptoms improve. Like blood pressure medication, antipsychotics improve symptoms only when taken consistently. Please note that the APA states that antipsychotic medications should be continued if they are working and adjusted only if not working.   

• • Typical antipsychotics: chlorpromazine (Thorazine), fluphenazine (Prolixin), haloperidol (Haldol), loxapine (Adusuve), molindone (Moban), perphenazine (Trilafon), pimozide (Orap), prochlorperazine (Compazine, Compro), thiothixene (Navane), thoridazine (Mellaril), trifluoperazine (Stelazine). 

• • Atypical antipsychotics: aripiprazole (Abilify), asenapine (Secuado), brexpiprazole (Rexulti), cariprazine (Vraylar), iloperidone (Fanapt, Zomaril), lumateperone (Caplyta), lurasidone (Latuda), olanzapine (Zyprexa), quetiapine (Seroquel), paliperidone (Invega), risperidone (Risperdal), ziprasidone (Geodon).  

Clozapine: A differently acting atypical antipsychotic, clozapine (Clozaril) is the only FDA-approved medication for treatment-resistant schizophrenia and may be effective where other medicines fail to reduce psychotic symptoms that contribute to aggression and/or suicide. For many years clozapine was limited in the U.S. by strict usage protocols, called REMS — Risk Evaluation and Mitigation Strategy, that ended Feb. 25, 2025.  

Slowly introducing clozapine (titration) helps to determine the optimal dose and minimize side effects, including known but rare risks for myocarditis (inflammation of the heart muscle) and neutropenia (too few of certain white blood cells). Often clozapine is tried as another medication is discontinued. Careful titration and a mix of the two during a transition phase is recommended by clozapine expert Dr. Robert Laitman.  

Long-Acting Injectables (LAIs): Used to treat psychosis in individuals with chronic schizophrenia or bipolar spectrum disorders, these medications may be injected into a muscle for gradual metabolizing. APA best-practice guidelines and global guidelines, INTEGRATE, recommend use of LAIs for people who need help with treatment adherence. Before starting an LAI, an individual might be prescribed an oral version of the medication to test effectiveness and tolerance.  

• • Options: fluphenazine decanoate (Prolixin), haloperidol decanoate (Haldol), flupentixol (Depixol), risperidone microspheres (Risperdol Consta), risperidone (Uzedy), aripiprazole monohydrate (Abilify Maintena), aripiprazole lauroxil (Aristada), olanzapine pamoate (Zyprexa Relprevv), paliperidone palmitate (Invega Sustenna, Trinza, or Hafyera). 

Mood stabilizers: Used to improve symptoms during acute manic, hypomanic, and mixed mood episodes and may also reduce symptoms of depression. Lithium was the first federally approved mood stabilizer and remains widely used under trade names such as Eskalith, Lithobid, and Lithonate. Some anti-anxiety and anti-convulsant medications also might be used to stabilize moods. 

Terms to know 

Adherence: A preferred term for describing a person’s willingness to accept and continue with treatment. New global guidelines for the treatment of schizophrenia, INTEGRATE, underscore the importance of addressing treatment adherence proactively by incorporating use of long-acting injectables (LAIs), plasma drug level testing, pill counts, and caregiver engagement and input. 

Dystonia: A side effect for some people using certain antipsychotic medications, dystonia causes involuntary muscle movements that resemble Parkinson’s symptoms. To alleviate this side effect, APA best-practice guidelines and global guidelines, INTEGRATE,  recommend use of an anticholinergic medication, which blocks certain neurotransmitters to prevent an overreaction of the parasympathetic nervous system, which is responsible for involuntary muscle movements. 

Electroconvulsive therapy (ECT): Brain stimulation may relieve severe symptoms of mood dysregulation but is usually only considered if an individual’s illness has not improved after other treatments such as medication or psychotherapy. In some situations, ECT is used for a rapid response, such as with suicide risk or catatonia (a state of unresponsiveness). 

Extrapyramidal symptoms: Medication-induced movement disorders that are most commonly caused by antipsychotic medications and other dopamine receptor-blocking agents. Early detection and treatment can reduce these symptoms, which are associated with treatment nonadherence.

Formularies: Drug formularies impact what medications are available to incarcerated patients. A formulary is a list of medications that prescribers contracted with or working within the facility may choose from. In some situations, a medication that didn’t make the list could be approved for use if the patient meets specific clinical criteria. Understanding what medications are specifically prescribed and why might help advocates make a case for someone who is incarcerated to keep taking a medication that has worked. 

Light therapy: Evidence-based to treat seasonal affective disorder (SAD), light therapy may benefit people with certain mood disorders if there is a seasonal worsening of depression in the winter or for milder forms of bipolar depression. 

Medication Assisted Treatment (MAT): Used to treat substance use disorder (SUD), drugs used for MAT might include methadone, naltrexone, and buprenorphine to reduce symptoms of withdrawal and craving.  

Polypharmacy: The practice of administering many different medicines concurrently, sometimes resulting in complicated side effects and/or adverse drug interactions.

Prior authorization: An insurance practice that requires a review of the request before a prescription is filled. Research shows that about a third of patients prescribed an antipsychotic have prescriptions rejected by a payer. Within six months, nearly half never get that medication and more than 10 percent never got any antipsychotic medicine. TAC’s article about insurance includes information about appealing a denial. 

Psychotherapy: Clinical therapies that may be used alone or alongside prescription medications include cognitive behavioral therapy (CBT), cognitive behavioral therapy for psychosis (CBTp), dialectical behavioral therapy (DBT), cognitive enhancement therapy (CET), motivational interviewing, family therapy, interpersonal therapy, and/or psychoeducation. 

Side effects: Impacts of medication that are unrelated to the therapeutic intention or benefit of the medication. Common side effects of antipsychotic medication include weight gain (addressed below); flat affect (lack of emotional expression); cognitive decline; tiredness; and movement disorders, including tardive dyskinesia and dystonia, defined within this list.  

Step therapy: A practice that requires a person to “fail” on one or more medications before trying a potentially more costly option that might be reimbursable through insurance. 

Substance use treatment: If SMI includes co-occurring symptoms of substance use disorder (SUD), combined care may be necessary. Medication assisted treatment (MAT) may be an important component of SUD treatment, especially for opioid use disorder.  

Tardive dyskinesia: A side effect for some people using certain antipsychotic medications, tardive dyskinesias are involuntary, repetitive body movements. Tardive dyskinesia is permanent and irreversible, which is one reason why it’s critical to monitor medications closely so that its development is detected quickly. To alleviate this side effect, APA best-practice guidelines recommend use of VMAT2 inhibitors (vesicular monoamine transporter-2 inhibitors), which are also used to treat movement disorders caused by Huntington’s disease.  

Titration: How medication dosages are gradually increased or decreased, often to manage potentially dangerous side effects from rapid introduction or withdrawal.  

Transcranial magnetic stimulation (TMS): This type of brain stimulation uses magnetic waves, rather than the electrical stimulus of ECT. TMS may relieve depression over a series of treatment sessions. Although not as powerful as ECT, TMS does not require general anesthesia and presents little risk of memory or adverse cognitive effects. 

Treatment resistance: Diagnosed when a patient does not respond to two typically prescribed medications for their condition. For example, if a client is prescribed a common antipsychotic and symptoms don’t improve over an extended amount of time, then another common antipsychotic fails after another extended amount of time, that patient has treatment resistance. Treatment resistance is medication-related and is different than “resistance to treatment,” which is most commonly associated with anosognosia, or lack of insight.  

What are options for treating the common side effect of weight gain? 

Antipsychotic medications are known for having metabolic effects, sometimes causing rapid and uncontrollable weight gain. This can discourage patients from wanting to maintain their treatment and lead to other health problems, including cardiovascular disease and/or diabetes.  

According to the new global initiative, INTEGRATE, “Metabolic monitoring is non-negotiable. The guideline mandates rigorous baseline and continuous monitoring of weight, waist circumference, blood pressure, glucose, lipids, and other vital markers. The team urges early intervention – focused on metformin initiation, lifestyle modification, or a change in antipsychotics — when weight gain or metabolic markers surge past established thresholds.”  

The guidelines further advise that caregivers regularly monitor side effects related to weight in order to promptly prescribe metformin and GLP-1 agonists (commonly used to treat type 2 diabetes) to support weight management.    

An article for Psychiatry Online discusses the issue in depth, offering these specific recommendations for providers:  

• • Avoid off-label use of antipsychotic medications when a name-brand version is more metabolically neutral and choose options with lower metabolic risk for clients prone to weight gain. 

• • Consider lowering the dosage or switching medications when there is evidence of significant metabolic impact, such as weight gain of seven percent of body weight or if blood fat lipids spike. 

How might I convince a loved one to take medication? 

When a person with SMI lacks insight into their condition, helping them understand that taking medication might improve their life circumstances can be difficult. Dr. Xavier Amador provides expert guidance about how you might motivate someone with anosognosia to engage with treatment. Visit the LEAP Institute for information and training. Here are some quick tips: 

• • You cannot win on the strength of your argument. You might win on the strength of your relationship. LEAP is about listening actively, showing empathy, agreeing (I wouldn’t want to take medicine either if I…), and seeking ways to partner. 

• • Language matters, so avoid words or phrases that imply a person is in denial or won’t comply. Instead, try to express and understand how a person cannot perceive their illness. They are unaware and do not understand their SMI.