INTRODUCTION Drug induced psychosis is also referred to as substance induced psychotic disorder or stimulant psychosis Most drugs of misuse are known for the feelings of euphoria, giddiness, laughter, etc. DIP is a mental health condition in which the onset of psychotic episodes or psychotic disorder symptoms can be traced to starting or stopping using alcohol or a drug (onset during intoxication or onset during withdrawal). Drug-induced psychosis is often caused by taking too much of a certain drug, so that its level of toxicity provokes paranoia and a psychotic episode. It can also occur if you have an adverse reaction from mixing different substances, or withdrawing from a drug, prescribed or otherwise .
DIP can either exacerbate or trigger the onset of mental illnesses such as bipolar disorder and schizophrenia due to being predisposed to the condition . Psychosis is often characterized by delusions or hallucinations, which are experiences that are far removed from reality . D IP is considered a psychiatric emergency, and these patients are usually hospitalized for safe detoxification and observation.
Epidemiology According to the DSM-V, between 7% and 25% of people presenting with an initial episode of psychosis have SIPD due to substance or medication use ( American Psychiatric Association , 2013). People with heavy substance use, especially marijuana, amphetamine , psychedelics, or cocaine are at highest risk (Aldandashi, 2009). Nevertheless, a wide range of substances and other conditions can produce psychosis( Caton , 2005; Sacks, 2012 ). Prescribed medications that cause psychosis include steroids and non-steroidal anti-inflammatory drugs, antiviral agents and antibiotics, anticholinergics, antihistamines , antiparkinsonian agents, muscle relaxants, opioids, and some psychotropic medications (e.g., antidepressants, anticonvulsants, and stimulants ).
Epidemiology Cannabis is the most widely used illicit substance in the world, with 6–7% of the population in Europe and 15.3% of the population in the USA using it each year ( World Drug Report 2019) According to United Nations Office on Drugs and Crime, in 2017 there were an estimated 28.9 million past-year users of amphetamine and methamphetamine (MA), corresponding to 0.6% of the global population aged 15–64, 15% lower than the previously estimated 34.2 million in 2016, with the form of the MA used varying considerably in different regions T here were an estimated 21.3 million past-year users of “ecstasy ,” corresponding to 0.4% of the global population aged 15–64. The annual prevalence of ketamine recreational use and abuse ranges from 0.8 to 1.8% in young adults
Causes and Risk Factors T ypically caused by the misuse of alcohol or drug; Drug potency, drug purity, and the amount of drug used. Some other risk factors may make one more prone to developing this type of disorder include: A traumatic brain injury or stroke A family or personal history of schizophrenia, mood disorders, or psychotic disorders Side effects of certain prescription medications Dementia, such as Alzheimer's disease Brain tumors, lesions, or cysts Genetic abnormalities
symptoms Hallucinations, including hearing, seeing, or smelling things that are not present Delusions, including hearing voices or believing that you're being watched Religious delusions, like thinking that a deity is sending you special messages Problems distinguishing between fantasy and reality, like imagining a special relationship with a celebrity Trouble taking care of yourself, including forgetting to eat and bathe, or hoarding things Paranoia and suspicion, including suspecting loved ones, institutions, or other people of harming you or being “out to get you” Difficulty communicating clearly, including disordered speech and thoughts Hypersensitivity to sounds, smells, or others sensory input A flat affect or lack of emotional expressions
Drugs that can cause psychosis Many recreational drugs and prescription drugs can induce psychosis symptoms that can mimic serious psychiatric disorders. It’s a psychotic episode that is related to the abuse of an intoxicant. It is associated with suicidal thoughts, dangerous and violent behavior, hospitalization and arrests. These include alcohol, benzodiazepines, methamphetamine, cocaine, amphetamine, ecstasy, ketamine, lysergic acid diethylamide, phencyclidine, opioids, butane, antihistamines, anticholinergics, anti-epileptics etc.
A lcohol Alcohol is one of the most commonly abused substances among individuals with schizophrenia Alcohol can cause delusions , mental confusion , disorganized speech, and disorientation. It can cause psychosis but only after days or weeks of intense use. Chronic alcohol abusers, for several years, are also vulnerable to intense paranoia and hallucinations. This occurs due to the damaging effects of alcohol on the brain, due to lack of thiamine in the body that can lead to Wernicke- korsakoff syndrome
Benzodiazepines Benzodiazepines and barbiturates cause psychotic symptoms in the event of overdoses as well as during withdrawal. Benzodiazepines are preferred for patients with severe anxiety. The onset of withdrawal symptoms in patients physically dependent on long –acting benzodiazepines can be delayed up to 7 days after discontinuation of the drug. A common approach in detoxification of such patients is to initiate treatment at usual dosages (chlordiazepoxide orallyn50mg three times a day; lorazepam orally 2 mg three times a day) and to maintain the initial dosage for 5 days , with gradual tapering over an additional 5 days. Symptoms – restlessness, akathisia, anxiety, blurred vision, chest pain
CNS STIMULANTS Methamphetamine It’s use can lead to paranoia, persecution delusions and auditory hallucinations These symptoms can subside after stopping use, but they can also persist for weeks or longer , and may increase one’s susceptibility for developing future psychosis. Even after long periods of abstinence, psychotic symptoms may return in periods of stress.
Cocaine Cocaine psychosis can occur in powdered cocaine users and the crack cocaine smokers. It may be more common among crack users but when a person gets his hands on a large quantity of powdered cocaine and binges non-stop for days, psychosis becomes a common symptom. Paranoia is a common symptom that accompanies heavy cocaine abuse. Other symptoms of cocaine toxicology include: hypertension, altered mental status, headache, epistaxis, confusion, excited delirium, extreme diaphoresis, hyperthermia etc.
Amphetamines This can cause psychotic symptoms similar to methamphetamine and cocaine after a repeated use. Amphetamines are highly addictive drugs. Amphetamines and methamphetamines act directly on the mesolimbic dopaminergic “reward system” by inducing release of dopamine, and to some extent norepinephrine, in the synaptic clefts of the nucleus accumbens and other terminal areas provoking a euphoric state, but also addictions. Symptoms include lack of concentration, delusions of persecution, increased motor activity, disorganization of thoughts, lack of insight, anxiety, suspicion and auditory hallucinations
Club/ recreational drugs (e.g. ecstasy) Methylenedioxymethamphetamine (MDMA), also called molly, Stacy, XTC, Adam, clarity. Ecstasy can cause psychotic symptoms, antisocial behavior, and panic attacks. Persistent psychosis has been reported after a single use in some people.
hallucinogens Ketamine It is believed that ketamine impacts both glutamatergic and dopaminergic function to provoke psychosis Already with schizophrenia or mental illness tend to experience more severe psychotic episodes after ingesting eve sub anesthetic doses of ketamine . Symptoms – delusions, cognitive impairments, disordered thinking, and incoherent
LSD(Lysergic Acid Diethylamide) Episodes of LSD induced psychosis are subject to significant individual variation. It is characterized by delirium, while others are more similar to schizophrenia. Deficient levels of CNS serotonin may be a causative factor. Successful treatment is seen when A serotonin precursor(L-5-hydroxytryptophan) i s administered
PCP(Phencyclidine) High doses and/or use PCP over a long-term may be more likely to become psychotic Symptoms – delusions of physical power, sensory alterations, time distortion, and bizarre experiences
INHALANTS BUTANE It can cause severe psychotic episodes among individuals with no previous psychiatric illness. It is more common among those that abuse butane , especially those that use it regularly over an extended time span. Butane-induced psychosis could produce symptoms like violence, persecutory delusions, and visual hallucinations.
opioids Opioid-psychosis is associated with opioid abuse/ withdrawal. It alters dopaminergic processing , which contributes to psychotic episodes. Nalbuphine shows psychotic symptoms, it is treated with administration of Naloxone. It is characterized by delirium. Heroin induced psychosis is rare but can occur under certain conditions like use during a period of heightened stress, mix it with other substances or have underlying mental condition. Heroin intoxication can cause delirium that progresses to psychosis. Heroin induced psychosis is most common in the form of heroin withdrawal psychosis. Mx – methadone , lofexinide , buprenorphine.
OVER THE COUNTER DRUGS(OTC) OTC medications have been associated with psychotic symptoms when taken at supratherapeutic doses They include; antihistamines, diphenhydramine, pheniramine, promethazine Symptoms – often include both auditory and visual hallucinations It can be mitigated by administration of physostigmine salicylate. This drug rapidly crosses the blood-brain-barrier and functions as a reversible acetylcholinesterase inhibitor, thus increasing levels of acetylcholine to decrease psychotic symptoms.
Dextromethorphan(DXM) Abusing cough syrup (with dxm) may experience psychotic episodes. Symptoms in DXM-induced psychosis include: bizarre feelings, dissociation, and paranoia. DXM-psychosis occurs as a result of its serotonergic and opiodergic effects.
Prescription Drugs Anticholinergics These have a tendency to cause psychotic episodes, when ingested at a high dosages. Examples – Atropine and Scopolamine It’s successfully treated by administering physiostigmine which acts as an acetylcholinesterase inhibitor, thus increasing acetylcholine levels, which counteracts the effects of anticholinergic drugs. Symptoms include :restlessness, excitement, hallucinations, elevated mood, disorientation, stupor, and possibly coma.
Antiepileptics They elicit psychotropic effects via alterations in GABAergic neurotransmission Phenytoin or zonisamide are more likely to induce psychosis than other drugs Additionally those that experienced complex partial seizures and a low level of intelligence were more likely to develop psychosis.
Corticosteroids Those utilizing corticosteroids like prednisolone may experience psychotic episodes Low levels of complement proteins, and low creatinine may also be influential factors. Symptoms subside on discontinuation Can be controlled by administering the drug at smaller increments.
Decarboxylase inhibitors Those that have Parkinson’s disease are commonly prescribed L-Dopa to increase low dopamine levels Most people tolerate L-Dopa well, some individuals end up experiencing psychosis as a result of the dopaminergic increase. Symptoms – paranoia, agitation, hallucinations(particularly visual), as well as delusions Seroquel have been administered at low doses with success for treating levodopa-induced psychosis.
Fluoroquinolones E.g. ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, moxifloxacin, pefloxacin, sparfloxacin. Causes damage to CNS and in some cases irreversible psychosis. Most people treated with fluoroquinolones do not experience psychosis, but it is important to be aware of the adverse reactions and the potential for permanent neurological changes as a result of treatment. The drug most commonly linked to psychosis is ciprofloxacin
It inhibits binding of GABA to the GABA receptors, leaving the nervous system in an excitatory state It can be mitigated by discontinuing medication or taking the minimal effective dose. Symptoms are: dizziness, restlessness, hallucinations, anxiety
MARIJUANA Psychosis purely induced by cannabis is rare However anyone can have a psychosis on marijuana if they ingest a large enough amount Two ingredients in marijuana, Tetrahydrocannabinol and Cannabidiol , have opposite effects on certain regions of the brain Tetrahydrocannabinol(THC) increases the brain processes that can lead to symptoms of psychosis Cannabidiol may negate such symptoms Symptoms include: hallucinations(auditory, visual, olfactory, tactile, taste), delusions(grandiose, paranoid), bizarre behavior and thoughts.
DIAGNOSIS Diagnosis should be based on history, physical and mental exam , and laboratory tests as indicated for drugs and medications use. Understanding the history of substance and medication use and recent changes in the pattern of use is important . Significant others may help to provide this history and provide information regarding whether or not the patient has experienced a month or more of abstinence and his or her condition during that time. This information will help to identify substance use as a primary cause of the psychosis.
DSM-V Criteria for drug induced psychotic disorder The symptoms are not better explained by a psychotic disorder ( schizophrenia, bipolar etc.) that is not medication induced Evidence from medical examination, lab results and patient history that psychotic symptoms developed during substance use, or within one month of withdrawal from a substance known to cause psychotic symptoms. Presence of delusions and/or hallucinations Psychotic symptoms do not occur during an episode of delirium Symptoms are causing significant distress and/or impairment in one’s daily life and ability to function.
According to the DSM-V (American Psychiatric Association, 2013 ),the diagnostic criteria include: A. Presence of one or both of the following symptoms: 1. Delusions 2. Hallucinations B. There is evidence from the history, physical examination, or laboratory findings of both (1) and (2): 1. The symptoms in Criterion A developed during or soon after substance intoxication or withdrawal or after exposure to a medication 2. The involved substance/medication is capable of producing the symptoms in Criterion A C. The disturbance is not better explained by a psychotic disorder that is not substance or medication-induced. Such evidence of an independent psychotic disorder could include the following: The symptoms preceded the onset of substance/medication use; the symptoms persist for a substantial period of time (e.g., about 1 month) after the cessation of acute withdrawal or severe intoxication; or there is other evidence of an independent non-substance/medication –induced psychotic disorder (e.g., a history of recurrent non-substance/medication-related episodes) D. The disturbance does not occur exclusively during the course of delirium E. The disturbance causes clinically significant distress or impairment in social, occupational, or other areas of functioning . ( DSM-5, American Psychiatric Association 2013, page 110)
Treatment Detoxification First, patient must stop using the drug. Patients in the emergency setting should be safely detoxified and carefully monitored by medical personnel . Inpatient treatment might be best choice if the condition is serious . Medication: antipsychotic drugs - When psychotic symptoms do not remit quickly, patients typically receive antipsychotic medications. other types of medication to help control your symptoms and treat other conditions that may be affecting you like anxiety, depression, or PTSD. psychotherapy: Therapy can be essential to helping you find out what triggers your episodes and how to handle your condition., Support: Finding the right support group can make a world of difference - especially if in recovery for drug or alcohol use. Talking to other people who have been in same shoes.
Long-term treatment . People with SIPD are a high-risk group, even if they do well over the first year after an initial psychotic episode. Several factors enhance relapse prevention and long-term recovery: safe housing, peer support for abstinence, employment, and careful follow-ups . As with other long-term illnesses, social determinants probably outweigh medical treatments in importance, and the provision of vocational, educational, housing , and peer supports may help to alleviate some of the risk associated with these social factors. Involvement in peer-support groups may also be beneficial. Treatment providers should do their best to maintain contacts with these patients and attend to their overall needs. When the diagnosis changes to non-affective psychosis, referral to early psychosis treatment programs may be optimal
Antipsychotics Are classified into: First-generation antipsychotics/ typical antipsychotics and second generation antipsychotics / atypical antipsychotics First-generation antipsychotics are dopamine receptor antagonists (DRA) They include phenothiazines (trifluoperazine, perphenazine, prochlorperazine, acetophenazine, triflupromazine, mesoridazine), butyrophenones (haloperidol), thioxanthenes (thiothixene, chlorprothixene), dibenzoxazepines (loxapine), dihydroindoles (molindone), and diphenylbutylpiperidines (pimozide ). Second-generation antipsychotics are serotonin-dopamine antagonists They include risperidone , olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, asenapine, lurasidone, iloperidone, cariprazine, brexpiprazole, and clozapine .
Caution is necessary when using first-generation antipsychotics in alcohol withdrawal and phencyclidine intoxication . Mechanism of Action The first-generation antipsychotics work by inhibiting dopaminergic neurotransmission; their effectiveness is best when they block about 72% of the D2 dopamine receptors in the brain. They also have noradrenergic, cholinergic, and histaminergic blocking action . Second-generation antipsychotics work by blocking D2 dopamine receptors as well as serotonin receptor antagonist action. 5-HT2A subtype of serotonin receptor is most commonly involved.
Administration First-Generation Antipsychotics All dopamine receptor antagonists are available and can be administered in oral form. Except for thioridazine, pimozide, and molindone, all other first-generation antipsychotics can also be given parenterally. Haloperidol and fluphenazine can be delivered in long-acting depot parenteral form. Second-Generation Antipsychotics T hese can be administered in oral or parenteral forms. Risperidone, olanzapine, aripiprazole, and paliperidone are available as extended-release or long-acting injectable forms. Clozapine, asenapine, and olanzapine are available in the sublingual formulation.
Side effects Dry mouth, blurred vision, flushing and constipation. These may ease off when you become used to the medicine. Drowsiness (sedation), which is also common but may be an indication that the dose is too high. A reduced dose may be an option. Weight gain which some people develop. Weight gain may increase the risk of developing diabetes and heart problems in the longer term. This appears to be a particular problem with the atypical antipsychotics - notably, clozapine and olanzapine. Movement disorders which develop in some cases. These include Parkinsonism - this can cause symptoms similar to those that occur in people with Parkinson's disease - for example, tremor and muscle stiffness. Akathisia - this is like a restlessness of the legs. Dystonia - this means abnormal movements of the face and body .
Tardive dyskinesia (TD) - this is a movement disorder that can occur if you take antipsychotics for several years. Neuroleptic malignant syndrome is a rare but fatal adverse effect that can occur at any time during treatment with FGAs. Though the risk of neuroleptic malignant syndrome is higher with first-generation antipsychotics, second-generation antipsychotics also cause this adverse effect . Atypical antipsychotic medicines are thought to be less likely to cause movement disorder side-effects than typical antipsychotic medicines. Atypicals do, however, have their own risks - in particular, the risk of weight gain
C ontraindications First-generation antipsychotics are contraindicated in the following situations: History of severe allergy Use of central nervous system (CNS) depressants like barbiturates, benzodiazepines, opioids With anticholinergic medication like scopolamine or the use of phencyclidine Severe cardiac abnormalities History of seizure disorder Narrow-angle glaucoma or prostatic hypertrophy History of or ongoing tardive dyskinesia
Second-generation antipsychotics carry the FDA boxed warning of increased incidence of stroke in elderly patients with dementia. The recommendation is to avoid the use of second-generation antipsychotics along with other drugs that prolong the QTc interval. Antipsychotics should be avoided during pregnancy, especially in the first trimester, and should be used only if the benefits outweigh the risks of treatment. Antipsychotics are secreted in breast milk, and it is advisable to avoid breastfeeding.
prognosis Drugs that induce psychosis usually have short term effects on an individual’s brain function and can last anywhere from 30 minutes to 24 hours. Short term drug induced psychosis symptoms are usually followed by drug withdrawal symptoms that resemble schizophrenic delusions and hallucinations . Some drug induced psychotic disorders resolve without treatment but other cases need medications to help relieve the delusions and hallucinations . Psychosis from drugs can become permanent. If drug induced psychosis is not treated, the person could experience a drug-induced form of schizophrenia, which will be a lifelong diagnosis .
In a study on Long-term follow-up of patients treated for psychotic symptoms that persist after stopping illicit drug use, by Xianhua Deng et all, revealed that in about 60% of cases psychotic symptoms resolved within one month of terminating illicit drug use, in about 30% of cases the psychotic symptoms persisted for 1 to 6 months after stopping illicit drug use and in about 10% of cases psychotic symptoms persisted for more than 6 months after stopping illicit drug use. Persistent psychotic symptoms were more common in those with a positive family history of mental illness, an earlier age of onset of illicit drug use and a longer history of illicit drug use. Almost 90% of the patients restarted illicit drug use at some point after treatment for their psychosis symptoms.