Almost all psychotropics have haematology- or biochemistry-related adverse effects that may be detected using routine blood tests. While many of these changes are idiosyncratic and not clinically significant, others, such as the agranulocytosis associated with agents such as clozapine, will require regular monitoring of the full blood count. In general, where an agent has a high incidence of biochemical/haematological adverse effects or a rare but potentially fatal effect, regular monitoring is required as discussed in other sections.
For other agents, laboratory-related adverse effects are comparatively rare (prevalence usually less than 1%), are often reversible upon cessation of the putative offending agent and are not always clinically significant. It should further be noted that medical comorbidity, polypharmacy and the effects of non-prescribed agents including substances of abuse and alcohol may also influence biochemical and haematological parameters. In some cases, where a clear temporal association between starting the agent and the onset of laboratory changes is unclear, then withdrawal and rechallenge with the agent in question may be considered. Where there is doubt as to the aetiology and significance of the effect, the appropriate source of expert advice should always be consulted.
Tables 15.1 and 15.2 summarise those agents with identified biochemical and haematological effects from information compiled from various sources.1, 2, 3, 4, 5, 6, 7, 8, 9 In many cases the evidence for these various effects is limited, with information obtained mostly from case reports, case series and information supplied by manufacturers. For further details about each individual agent, the reader is encouraged to consult the appropriate section of this book as well as other specialist sources, particularly product literature relating to individual drugs.
Table 15.1 Summary of Biochemical Changes Associated with Psychotropics.
| Parameter | Reference range10 | Agents reported to raise levels | Agents reported to lower levels |
|---|---|---|---|
| Alanine aminotransferase (ALT) | F: ≤34U/L M: ≤45U/L (may be higher in obesity) | Antipsychotics: asenapine, benperidol, cariprazine, clozapine, haloperidol, loxapine, lumateperone tosylate, olanzapine, phenothiazines, quetiapine, risperidone/paliperidone Antidepressants: agomelatine, bupropion, MAOIs, mianserin, mirtazapine, SNRIs, SSRIs (especially paroxetine and sertraline), TCAs, trazodone, vortioxetine Anxiolytics/hypnotics: barbiturates, benzodiazepines, buspirone, clomethiazole, promethazine, suvorexant, tasimelteon, zolpidem Mood stabilisers: carbamazepine, lamotrigine, valproate Other: alcohol, atomoxetine, beta-blockers, caffeine, cocaine, disulfiram, naltrexone, opioids, stimulants (abused) | Vigabatrin |
| Albumin | 35-50g/L (gradually decreases after age 40) | Microalbuminuria may be a feature of metabolic syndrome secondary to psychotropic use (especially phenothiazines, clozapine, olanzapine and possibly quetiapine) | Chronic use of amfetamine or cocaine |
| Alkaline phosphatase | 50-120U/L | Baclofen, beta-blockers, benzodiazepines, caffeine (excess/chronic use), carbamazepine, citalopram, clozapine, disulfiram, duloxetine, galantamine, haloperidol, loxapine, memantine, modafinil, nortriptyline, olanzapine, phenytoin, sertraline, topiramate, trazodone, valbenazine, valproate; also associated with agents causing NMS | Buprenorphine, fluoxetine (in children), zolpidem (rarely) |
| Ammonia | 11-32µmol/L (increased following meals and exercise) | Barbiturates, carbamazepine, tobacco smoking, topiramate, valproate (may present with signs of encephalopathy) | None known |
Amylase | 28-100U/L | Alcohol (acute), donepezil, opioids, pregabalin, rivastigmine, SSRIs (rarely) Agents associated with pancreatitis: alcohol, carbamazepine, clozapine, olanzapine, valproate | None known |
Aspartate aminotransferase (AST) | F: ≤34U/L M: ≤45U/L | As for ALT; baclofen. Note: ALT is preferred as an indicator of liver damage | Trifluoperazine, vigabatrin |
| Bicarbonate | 22-29mmol/L | Laxative abuse | Agents associated with SIADH: all antidepressants, antipsychotics (clozapine, haloperidol, olanzapine, phenothiazines, pimozide, risperidone/paliperidone, quetiapine); carbamazepine; also associated with agents causing metabolic acidosis (alcohol, cocaine, topiramate, zonisamide) |
| Bilirubin | ≤21µmol/L (total) | Amitriptyline, atomoxetine, benzodiazepines, carbamazepine, chlordiazepoxide, chlorpromazine, citalopram, clomethiazole, clozapine, disulfiram, fluphenazine, imipramine, lamotrigine, meprobamate, milnacipran, olanzapine, phenothiazines, phenytoin, promethazine, sertraline, valbenazine, valproate; also associated with agents causing cholestasis/hepatic damage | Barbiturates |
| C-reactive protein | <10mg/L | Buprenorphine (rare); also associated with agents causing myocarditis (clozapine) | None known |
| Calcium | 2.20-2.60mmol/L (total, adjusted) 1.15-1.34mmol/L (ionised) | Lithium (rare) | Barbiturates, carbamazepine, haloperidol, valproate |
| Carbohydrate-deficient transferrin (CDT) | ≤1.5% | Alcohol (CDT levels of 1.6-1.9% suggest high intake; levels ≥2% suggest excessive intake) | None known |
| Chloride | 95-108mmol/L | Agents causing hyperchloraemic metabolic acidosis: topiramate, zonisamide | Medications associated with SIADH: all antidepressants, antipsychotics (clozapine, haloperidol, olanzapine, phenothiazines, pimozide, risperidone/paliperidone, quetiapine); carbamazepine, laxative abuse |
| Cholesterol (total) | ≤5.2mmol/L (usually compared with recommended action limits rather than reference ranges) | Antipsychotics, especially those implicated in the metabolic syndrome (clozapine, olanzapine, phenothiazines, quetiapine). Rarely: aripiprazole, beta-blockers (additive effects with clozapine), carbamazepine, disulfiram, duloxetine, memantine, mirtazapine, modafinil, phenytoin, rivastigmine, sertraline, venlafaxine | Prazosin, thyroid agents |
| Creatine kinase | F: 25-200U/L M: 40-320U/L (range for people of European descent; may be higher in other ethnic groups) | Bremelanotide, brexpiprazole, cariprazine, clonidine, clozapine (when associated with seizures), cocaine, dexamfetamine, donepezil, lumateperone, olanzapine, pregabalin; also associated with agents causing NMS and SIADH; agents administered intramuscularly | None known |
| Creatinine | F: 55-100µmol/L M: 60-120µmol/L | Clozapine, lithium, lurasidone, thioridazine, valproate; medications associated with rhabdomyolysis (benzodiazepines, dexamfetamine, pregabalin, thioridazine); also associated with agents causing renal impairment, NMS and SIADH | None known |
| Ferritin | F: 15-150mcg/L M: 30-400mcg/L (increases with age) | Alcohol (acutely and in alcoholic liver disease) | None known |
| Gamma-glutamyl transferase (GGT) | F: ≤38U/L M: ≤55U/L (limits twofold higher in persons of African ancestry) | Antidepressants: mirtazapine, SSRIs (paroxetine and sertraline implicated), TCAs, trazodone, venlafaxine Anticonvulsants/mood stabilisers: carbamazepine, lamotrigine, phenobarbitone, phenytoin, valproate Antipsychotics: benperidol, chlorpromazine, clozapine, fluphenazine, haloperidol, olanzapine, quetiapine Other: alcohol, barbiturates, clomethiazole, dexamfetamine, modafinil, tobacco smoking | None known |
| Glucose | Fasting: 2.8-6.1mmol/L Random: <11.1mmol/L | Antidepressants: MAOIs, SSRIs/SNRIs, TCAs Antipsychotics: chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine and others Substances of abuse: amfetamine, methadone, opioids Other: baclofen, beta-blockers, bupropion, caffeine (in diabetics), clonidine, dexmedetomidine, donepezil, gabapentin, galantamine, lithium, nicotine, sympathomimetics, thyroid agents, valbenazine | Alcohol; rarely with duloxetine, haloperidol, pregabalin, TCAs Medications associated with metabolic syndrome may result in raised or decreased glucose levels |
| HbA1c | 20-39mmol/mol | Lithium, MAOIs, SSRIs | |
| Lactate dehydrogenase | 90-200U/L (levels rise gradually with age) | Benzodiazepines, clozapine, methadone, TCAs (especially imipramine), valproate; also associated with agents causing NMS | None known |
| Lipoproteins: HDL | >1.2mmol/L | Carbamazepine, nicotine, phenobarbital, phenytoin | Beta-blockers, olanzapine, phenothiazines, valproate |
| Lipoproteins: LDL | <3.5mmol/L | Beta-blockers, caffeine (controversial), carbamazepine, chlorpromazine, clozapine, iloperidone, memantine, mirtazapine, modafinil, olanzapine, phenothiazines, quetiapine, risperidone/paliperidone, rivastigmine, venlafaxine | Prazosin |
| Phosphate | 0.8-1.5mmol/L | Dexamfetamine; also associated with agents causing NMS | Carbamazepine, lithium, mianserin, topiramate |
| Potassium | 3.5-5.3mmol/L | Beta-blockers, lithium | Alcohol, disulfiram, caffeine, cocaine, haloperidol, lithium, mianserin, pregabalin, reboxetine, rivastigmine, sodium oxybate, sympathomimetics, topiramate, zonisamide; may also be a feature of delirium tremens |
| Prolactin | Normal: <350mU/L Abnormal: >600mU/L | Antidepressants: especially amoxapine, MAOIs and TCAs; SSRIs and venlafaxine also implicated Antipsychotics: amisulpride, haloperidol, pimozide, risperidone/paliperidone, sulpiride and others (aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, lurasidone, olanzapine, quetiapine and ziprasidone have minimal effects on prolactin levels) Other: benzodiazepines, buspirone, deutetrabenazine, opioids, ramelteon, tetrabenazine, valbenazine | Aripiprazole, dopamine agonists, pirenzepine |
| Protein (total) | 60-80g/L | None known | Olanzapine (rarely) |
| Sodium | 133-146mmol/L | Lithium (in overdose) | Antidepressants: especially SSRIs/SNRIs; others also implicated - see section on hyponatraemia in Chapter 3 Antipsychotics: all (via SIADH) Mood stabilisers: carbamazepine, lithium, valproate Other: benzodiazepines, clonidine, donepezil, memantine, rivastigmine |
| Testosterone | F: 0.22-2.9nmol/L M: 9.9-27.8nmol/L | Diazepam | Opioids, ramelteon |
| Thyroid-stimulating hormone | 0.3-4.0mU/L | Aripiprazole, carbamazepine, lithium, quetiapine, rivastigmine, sertraline, valproate (slightly) | Moclobemide, thyroid agents |
| Thyroxine | Free: 9-26pmol/L Total: 60-150nmol/L | Rarely; amfetamine (heavy abuse), moclobemide, propranolol | Barbiturates, carbamazepine, liothyronine, lithium (causes decreased T4 secretion), opioids, phenytoin, valproate. Rarely implicated: aripiprazole, clozapine, quetiapine, rivastigmine, sertraline |
| Triglycerides | None known | ||
| Triiodothyronine | Free: 3.0-6.8pmol/L Total: 1.2-2.9nmol/L | Heroin, methadone | Free T3: valproate Total T3: carbamazepine, lithium, propranolol |
| Urate (uric acid) | F: 0.16-0.36mmol/L M: 0.21-0.43mmol/L (increases with age) | Alcohol (acute), caffeine (false positive), clozapine, levodopa, olanzapine, pindolol, prazosin, topiramate, zonisamide | Sertraline (slightly) |
| Urea | 2.5-7.8 mmol/L (increases with age) | Carbamazepine, levodopa; rarely with agents associated with anticonvulsant hypersensitivity syndrome and rhabdomyolysis | None known |
May also be associated with hypoglycaemia.
May also be associated with subnormal prolactin levels.
F, female; HbA1c, haemoglobin A1c; HDL, high-density lipoprotein; LDL, low-density lipoprotein; M, male; MAOIs, monoamine oxidase inhibitors; NMS, neuroleptic malignant syndrome; SIADH, syndrome of inappropriate antidiuretic hormone; TCAs, tricyclic antidepressants.
Table 15.2 Summary of Haematological Changes Associated with Psychotropics.
| Parameter | Reference range | Agents reported to raise counts/levels | Agents reported to lower counts/levels |
|---|---|---|---|
| Activated partial thromboplastin time | 23-33 seconds | Phenothiazines (especially chlorpromazine) | Modafinil (rare) |
| Basophils | 0.0-0.1×109/L | Clozapine, TCAs (especially desipramine) | None known |
| Eosinophils | 0.04-0.40×109/L | Amoxapine, beta-blockers, bupropion, buspirone, carbamazepine, chloral hydrate, chlorpromazine, clonazepam, clozapine, donepezil, fluphenazine, haloperidol, loxapine, meprobamate, maprotiline, methylphenidate (IV abuse only), modafinil, naltrexone (parenterally administered), olanzapine, promethazine, quetiapine, risperidone/paliperidone, SSRIs, TCAs, tetrazepam, tryptophan, valproate, venlafaxine; may also be a feature of agents causing a hypersensitivity syndrome | None known |
| Erythrocyte sedimentation rate | F: 1-12mm/h M: 1-10mm/h (increases with age) | Clozapine, dexamfetamine, levomepromazine, maprotiline, SSRIs | Buprenorphine |
| Haemoglobin | F: 115-165g/L M: 130-180g/L | Clozapine, testosterone, tobacco smoking | Aripiprazole, barbiturates, buprenorphine, bupropion, carbamazepine, chlordiazepoxide, chlorpromazine, donepezil, duloxetine, galantamine, MAOIs, memantine, meprobamate, mianserin, phenytoin, promethazine, rivastigmine, tramadol, trifluoperazine, vigabatrin |
| Lymphocytes | 1.5-4.5×109/L | Naltrexone, opioids, tobacco smoking, valproate; may also be a feature of drugs causing hypersensitivity syndrome | Alcohol (chronic), chloral hydrate, clozapine, lithium, mirtazapine (rarely) |
| Mean cell haemoglobin | 27-32pg | Medications associated with megaloblastic anaemia, e.g. all anticonvulsants, nitrous oxide | None known |
| Mean cell haemoglobin concentration | 320-360g/L | ||
| Mean cell volume | 80-100fL | Alcohol | |
| Monocytes | 0.2-0.8×109/L | Haloperidol | None known |
| Neutrophils | 2.0-7.5×109/L (may be lower in people of African descent owing to benign ethnic neutropenia) | Bupropion, carbamazepine, citalopram, chlorpromazine, clozapine, duloxetine, fluoxetine, fluphenazine, haloperidol, lamotrigine, lithium, maprotiline, olanzapine, quetiapine, risperidone/paliperidone, rivastigmine, tiotixene, trazodone, venlafaxine | Agents associated with agranulocytosis: amoxapine, aripiprazole, barbiturates, carbamazepine, chlordiazepoxide, chlorpromazine, clozapine, cocaine (adulterated), diazepam, fluphenazine, haloperidol, meprobamate, mianserin, mirtazapine, olanzapine, pirenzepine, promethazine, risperidone/paliperidone, TCAs (especially imipramine), tranylcypromine, valproate Agents associated with leucopenia: amitriptyline, amoxapine, asenapine, bupropion, carbamazepine, cariprazine, chlorpromazine, citalopram, clomipramine, clonazepam, clozapine, duloxetine, fluoxetine, fluphenazine, galantamine, haloperidol, lamotrigine, lorazepam, lumateperone, lurasidone, memantine, meprobamate, mianserin, mirtazapine, modafinil, nitrous oxide, olanzapine, oxazepam, phenelzine, pregabalin, promethazine, quetiapine, tranylcypromine, valproate, venlafaxine, ziprasidone Agents associated with neutropenia: clozapine, sertraline, trazodone, valproate |
| Packed cell volume | F: 0.37-0.47L/L M: 0.40-0.52L/L | Clozapine (rare), testosterone | Benzodiazepines (rare), buprenorphine, naltrexone, vigabatrin |
| Platelets | 150-450×109/L | Lamotrigine, lithium | Alcohol, barbiturates, beta-blockers, benzodiazepines, bupropion, buspirone, carbamazepine, chlordiazepoxide, chlorpromazine, clonazepam, clonidine, clozapine, cocaine, diazepam, donepezil, duloxetine, fluoxetine, fluphenazine, lamotrigine, meprobamate, methadone, methylphenidate, mirtazapine, naltrexone, nitrous oxide, olanzapine, pirenzepine, promethazine, quetiapine, risperidone/paliperidone, rivastigmine, sertraline, TCAs, tranylcypromine, trazodone, trifluoperazine, valproate, venlafaxine, ziprasidone; may also be a feature of drugs causing hypersensitivity syndrome Agents associated with impaired platelet aggregation: chlordiazepoxide, citalopram, diazepam, fluoxetine, fluvoxamine, paroxetine, piracetam, sertraline, valproate |
| Prothrombin time (PT)/international normalised ratio (INR) | PT: 10-13 seconds INR: 0.8-1.2 | Chloral hydrate, disulfiram, fluoxetine, fluvoxamine, mirtazapine, valproate; also agents interacting with warfarin | Barbiturates, carbamazepine, phenytoin, tiotixene |
Red blood count | F: 3.8-5.8×1012/L M: 4.5-6.5×1012/L | Lithium, testosterone | Buprenorphine, carbamazepine, chlordiazepoxide, chlorpromazine, donepezil, haloperidol, meprobamate, phenytoin, quetiapine, trifluoperazine |
| Red cell distribution width | 11.5-14.5% | Agents associated with anaemia, e.g. carbamazepine, chlordiazepoxide, citalopram, clonazepam, diazepam, lamotrigine, memantine, mirtazapine, sertraline, tranylcypromine, trazodone, valproate, venlafaxine | None known |
| Reticulocyte count | 0.5-2.5% (or 50-100×109/L) | None known | Carbamazepine, chlordiazepoxide, chlorpromazine, meprobamate, phenytoin, trifluoperazine Agents associated with pure red cell aplasia: carbamazepine, clozapine, valproate |
Previous reports of eosinophilia-myalgia syndrome may have been due to a contaminant from a single manufacturer.
May raise or lower levels.
Note that in rare cases clozapine has been associated with a ‘morning pseudo-neutropenia' with lower levels of circulating neutrophil levels. As neutrophil counts may follow circadian rhythms, repeating the FBC at a later time of day may be instructive.
F, female; M, male; MAOIs, monoamine oxidase inhibitors; TCAs, tricyclic antidepressants.