Schizophrenia is positive, negative and cognitive symptoms, and treating the positive ones does not fix the rest. Do not keep raising the antipsychotic for negative symptoms: most antipsychotics can worsen them, so reach for psychosocial treatment, and consider clozapine, which actually helps.
Why they matter
Schizophrenia is a syndrome of positive, negative and cognitive symptoms. Stopping the hallucinations does not mean your job is done.
“schizophrenia is a syndrome that comes with positive symptoms, negative symptoms, and cognitive symptoms. So when you're treating schizophrenic patients, you're not just stopping hallucinations and then saying your job's done”
10:38Top 10 Things to Know About ClozapineDec 2025 Clear disorganized behavior or speech, thought disorganization and negative symptoms are what make us reasonably sure a primary psychotic disorder is present.
“when we're reasonably sure that we have evidence to support a primary psychotic disorder of some kind, you know. And for me, it's when you see clear disorganized behaviors or speech. thought disorganization, right, and if you also see negative symptoms”
27:01What is Psychosis? Look at the DSM, Common Mimics, and a Framework for the DifferentialJan 2026 Without negative symptoms or disorganization, diagnosis is harder: many patients with delusions and hallucinations will not report the hallucinations or do not perceive them as hallucinations, so all you are left with is the delusions.
“for people who have primarily delusions and hallucinations without negative symptoms or disorganization, Many of them will not tell you about the hallucinations or they don't perceive the hallucinations to be hallucinations. So all you're left with is delusions”
13:39What is Psychosis? Look at the DSM, Common Mimics, and a Framework for the DifferentialJan 2026
Treatment approach
Treating the positive symptoms does not make the other symptoms fix themselves, so address them separately. Do not just keep increasing the antipsychotic hoping they improve; use psychosocial interventions aimed directly at them.
“with schizophrenia, if you treat the positive symptoms, it's not like the other things kind of fix in themselves. So you really do address those things separately”
32:43What is Psychosis? Look at the DSM, Common Mimics, and a Framework for the DifferentialJan 2026 Also said in 1 more episode
“don't just keep increasing the antipsychotic, hoping that those things can improve. Instead, start thinking of psychosocial interventions to directly address those things”
34:07What is Psychosis? Look at the DSM, Common Mimics, and a Framework for the DifferentialJan 2026 Most antipsychotics worsen negative symptoms, which we call neurolepsis. Clozapine actually helps in that regard.
“most of the other antipsychotics cause problems with regards to the fact they worsen negative symptoms, something that we call neurolepsis. So clozapine actually helps in that regard”
10:03Top 10 Things to Know About ClozapineDec 2025 Perphenazine is surprisingly decent at negative symptoms, with less EPS and akathisia than haloperidol or fluphenazine, a cleaner metabolic profile and minimal weight gain, though still a moderate EPS risk.
“So you get less of the EPS and the akathisia of haloperidol or the fluphenazine, which are the high-potency first-gen antipsychotics. Metabolic, be a little bit cleaner. Minimal weight gain, but still, you do get the moderate EPS risk. Actually, surprisingly decent at negative symptoms”
1:12:44Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 Cariprazine's D3 partial agonism might be helpful for negative symptoms.
“Cariprazine has D3 partial agonism. For some reason, the D3, even though I have no idea what D3 actually does, helps you remember it might be helpful for negative symptoms”
43:50Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026
Pitfalls
What looks like a patient's baseline may be sedation. When we brought sedation down a little, some patients almost changed personality; one worried she was getting manic, but she was just getting back to normal.
“I thought their baseline was their baseline, but once we tried bringing down the sedation a little bit, they almost changed their personality a bit. One of them even got worried was getting manic, but no, she was just getting back to normal”
Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025
It also comes up on
- PTSDReserve 'delusions', 'hallucinations', 'negative symptoms' and 'disorganization' for primary psychotic disorders. For trauma and personality syndromes say reported voices, fear or hypervigilance, and overvalued idea or inflexible belief.
- PsychosisReserve delusions, hallucinations, negative symptoms and disorganization for primary psychotic disorders, and use neutral descriptive language until you have a reasonable degree of medical certainty.
- AntipsychoticsDo not chase voices by raising the dose. The target is function, not zero voices; going high enough to remove them often means intolerable side effects or drug-induced negative symptoms, and trauma-related voices that are not dangerous usually just get over-sedated.
- HallucinationsDo not chase the voice. Getting rid of it often takes an antipsychotic dose high enough to cause intolerable side effects or drug-induced negative symptoms. Aim for function.
- PsychosisIn the DSM, psychosis is more than delusions and hallucinations: it includes disorganized speech, disorganized behavior and negative symptoms. Catatonia sits nearby but is not only seen in psychosis.
- SchizophreniaDSM psychosis is more than delusions and hallucinations: it includes disorganized speech, disorganized behavior and negative symptoms, and catatonia, which is not seen only in psychosis.
- SchizophreniaIn our clinical, non-scientific experience, long-term substance-induced psychosis has more positive than negative symptoms. In the end, what matters most is not what caused it but what will help treat it.
- Substance-induced psychosisIn our clinical, non-scientific experience, long-term substance-induced psychosis has more positive than negative symptoms. In the end, the question is less what caused it than what will help treat it.
From these episodes
- Antipsychotic Tier List: Ranking the Best and Worst Anti-psychoticsOct 2026 · 2 points
- What is Psychosis? Look at the DSM, Common Mimics, and a Framework for the DifferentialJan 2026 · 4 points
- Top 10 Things to Know About ClozapineDec 2025 · 2 points
- Choosing Antipsychotics in Schizophrenia: Side-Effects, Maximizing Efficacy, and Finding the Right Medication | Episode 17Feb 2025 · 1 point
Every point above is something said on the Psychofarm podcast, with the words as spoken and a link to the moment in the episode. It is education, not medical advice, and an episode reflects what we thought when we recorded it.